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Review

Biosynthesis and Production of Class II Bacteriocins of Food-Associated Lactic Acid Bacteria

1
College of Food Science and Engineering, Northwest A&F University, Xianyang 712100, China
2
College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Submission received: 18 April 2022 / Revised: 1 May 2022 / Accepted: 5 May 2022 / Published: 10 May 2022
(This article belongs to the Section Microbial Metabolism, Physiology & Genetics)

Abstract

:
Bacteriocins are ribosomally synthesized peptides made by bacteria that inhibit the growth of similar or closely related bacterial strains. Class II bacteriocins are a class of bacteriocins that are heat-resistant and do not undergo extensive posttranslational modification. In lactic acid bacteria (LAB), class II bacteriocins are widely distributed, and some of them have been successfully applied as food preservatives or antibiotic alternatives. Class II bacteriocins can be further divided into four subcategories. In the same subcategory, variations were observed in terms of amino acid identity, peptide length, pI, etc. The production of class II bacteriocin is controlled by a dedicated gene cluster located in the plasmid or chromosome. Besides the pre-bacteriocin encoding gene, the gene cluster generally includes various combinations of immunity, transportation, and regulatory genes. Among class II bacteriocin-producing LAB, some strains/species showed low yield. A multitude of fermentation factors including medium composition, temperature, and pH have a strong influence on bacteriocin production which is usually strain-specific. Consequently, scientists are motivated to develop high-yielding strains through the genetic engineering approach. Thus, this review aims to present and discuss the distribution, sequence characteristics, as well as biosynthesis of class II bacteriocins of LAB. Moreover, the integration of modern biotechnology and genetics with conventional fermentation technology to improve bacteriocin production will also be discussed in this review.

1. Introduction

Lactic acid bacteria (LAB) constitute a ubiquitous bacterial group that is widespread in niches of fermented food and gastrointestinal tracts of humans and many animals [1]. LAB are especially known for their ability to produce lactic acid as the main end-product. These microorganisms also possess the ability to synthesize a wide variety of bioactive metabolites, belonging to different classes of chemicals including diacetyl, hydrogen peroxide, antibiotics, and bacteriocins. Bacteriocins are ribosomally synthesized, extracellularly released bioactive peptides which have a bactericidal or bacteriostatic effect on other closely related species [2]. Bacteriocins from LAB have been used as food preservatives due to their heat stability and safety. Nisin is the most famous and best-studied bacteriocin, and it has high antibacterial activity against a wide range of Gram-positive bacteria. Nisin has received considerable attention in the food industry because it is the only purified bacteriocin approved for food use by the FDA and EU. However, several restrictions to the efficacy of nisin limit its range of practical applications. For instance, nisin has weak inhibition activity against Gram-negative bacteria, and its biological activity is reduced at an elevated pH. Moreover, spontaneous nisin resistance may occur in target bacteria. Consequently, lots of researchers seek to find novel bacteriocins with different targeting spectra and biochemical properties.
Bacteriocins produced by LAB are classified into two main classes: class I, containing heavily modified (lanthionine-containing) peptides called lantibiotics; and class II, containing non-modified peptides or peptides with minor modifications [3]. Class II bacteriocins are typically small (<60 amino acids) and heat-stable, and often synthesized as pre-bacteriocins containing an N-terminal leader sequence that is cleaved during secretion [4]. The class II bacteriocins are perhaps the best characterized and the most distributed group in food-associated LAB.
A typical gene cluster involved in the biosynthesis of class II bacteriocins consists of genes that encode a bacteriocin precursor peptide, an immunity protein, and an ATP-binding cassette (ABC) transporter. In some class II bacteriocins, an accessory protein is required for proper transportation [5]. The gene-encoded nature of bacteriocins makes them easily amenable through bioengineering to either increase their activity or specify target microorganisms. Concomitantly with the discovery of new bacteriocins, several interesting aspects of the biosynthetic mechanisms of class II bacteriocins have been revealed. These include regulation of the production, immunity (self-protection), and extracellular transportation.
Given the extensive fundamental and industrial importance of class II bacteriocins of LAB, the understanding of their distribution, biosynthesis, and genetics is beneficial for both scientific and industrial purposes. In this review, we investigate the distribution of class II bacteriocins in food-associated LAB. We then summarize the current understanding of the biosynthesis process of class II bacteriocins and the structure of their biosynthetic gene clusters. We also discuss the fermentation and genetic engineering strategies that can improve the yields of class II bacteriocins.

2. Classification of LAB Bacteriocins

There are several classification schemes based on the biochemical and structural features of LAB bacteriocins. In 1993, Klaenhammer et al. suggested a classification system that divides LAB bacteriocins into four groups [6]. The class I bacteriocins are lantibiotics, which are small membrane-active peptides (<5 kDa) containing uncommon amino acids such as lanthionine, β-methyl lanthionine, and dehydrated residues. Class II includes small heat-stable peptides without lanthionine residues. Class III comprises large heat-labile proteins, while class IV is composed of large peptides complexed with carbohydrates or lipids. Cotter et al. (2005) performed a thorough modification of Klaenhammer’s classification scheme and they grouped bacteriocins into just two categories: lantibiotics (class I) and non-lanthionine-containing bacteriocins (class II). They also suggested that the high-molecular weight thermolabile peptides (previously class III) should be designated as “bacteriolysins”, and the previous class IV should be extinguished [7]. Cotter’s classification scheme was broadly accepted for a long time, and has continuously been modified by researchers, since the repertoire of bacteriocins is rapidly growing [8,9,10].
In general, class I bacteriocins are produced as precursor peptides that undergo extensive post-translational modifications. The mature peptides contain unusual amino acids, such as 2,3-didehydroalanine, D-alanine, and 2,3-didehydrobutyrine, as well as characteristic lanthionine rings that result from thioether formation between the side chains of cysteine and serine or threonine. Class Ia bacteriocins, which include nisin, consist of cationic and hydrophobic peptides that form pores in target membranes and have a flexible structure compared to the more rigid class Ib. Class Ib bacteriocins, which are globular peptides, have no net charge or a net negative charge. Class Ic is a growing class of two-component lantibiotic systems that utilize two peptides that are each posttranslationally modified to an active form and act in synergy to provide antibacterial activity. More detailed information on the structure and biosynthesis of lantibiotics is presented in previous reviews [11,12,13].
Class II bacteriocins are a class of small non-lanthionine-containing peptides. Unlike the lantibiotics described above, class II bacteriocins are less modified; a disulfide bridge and some N-terminal modifications are known to exist in some class II bacteriocins. Class II bacteriocins are divided into four subclasses, IIa, IIb, IIc, and IId. Subclass IIa bacteriocins are the most thoroughly studied. They are also known as pediocin-like peptides with antilisterial activity [14]. The class IIb bacteriocins (two-peptide bacteriocins) require two different peptides for optimal activity [15]. Class IIc bacteriocins are referred to as circular bacteriocins whose ring structure is formed in a head-to-end fashion [16]. Class IId bacteriocins are categorized as bacteriocins that have no significant sequence similarity to the other class II bacteriocins [17].

3. Sequence Properties of Identified Class II Bacteriocins

Class II is the largest group of bacteriocins and includes a range of small peptides with antimicrobial activity. Great efforts have been made to identify the sequence of class II bacteriocins that LAB can produce and to further recognize the bases of their antibacterial activity. Nonetheless, sequence diversification can be found among class II bacteriocins. On the one hand, some motifs are conserved throughout evolution, such as the “YGNGV” motif in class IIa and the “GXXXG-like” motif in class IIb (Table 1). On the other hand, class IIc bacteriocins have poor sequence similarity but share similar structural patterns of globular arrangement of four or five helices (Table 1 [18]).
The leader is almost exclusively a so-called double-glycine type with exceptions for some bacteriocins that use a common Sec signal sequence for secretion [100] (Table 1). It is reported that the interaction of the positively charged amino acids of class II bacteriocins and negatively charged phospholipid molecules on the cell membrane is crucial for their bactericidal activity [14]. It is noteworthy that some newly identified class II bacteriocins have net zero or negative charges, e.g., lactococcin MMFII produced by Lc lactis, mutacin IV produced by Streptococcus mutans (Table 2 [18]). In most class IIa, class IIb, and class IId bacteriocins, small amino acids including glycine, alanine, and serine are present in high amounts, which increase the conformational freedom of bacteriocins. The high content of non-polar and aromatic amino acids will facilitate the interaction of bacteriocins with the cell membrane of the target bacteria (Table 2).

4. Distribution of Class II Bacteriocins in Food-Associated LAB

4.1. Approaches for Studying Bacteriocin Diversity

Bacteriocins must be obtained in their purified form to be studied and characterized. To develop novel food preservatives, many class II bacteriocins were purified and characterized from food-associated LAB strains, which have been isolated from a variety of food products of industrial and natural origins: mainly from meat and dairy products, but also vegetables. LAB in the family of Lactobacillus spp., Enterococcus spp., Pediococcus spp., Leuconostoc spp., were frequently identified as producers of class II bacteriocin. However, it is well known that establishing a purification system for bacteriocins can be expensive, time-consuming, and tedious. Moreover, in many cases, these systems often identify previously reported bacteriocins [101]. Another obstacle with the conventional approach is that bacteriocin production is often an unstable trait. The instability can be explained by the loss of plasmid-encoded traits, gene inactivation by transposition, or complex regulatory mechanisms that are affected by environmental factors [102].
It has been shown that the gene content and organization of bacteriocin are conserved among phylogenetically different bacteria. For instance, most class II bacteriocin precursors have the double-glycine motif in their leader sequence. This motif serves as a processing site by dedicated downstream transport machinery to cleave off the leader peptide concomitant with transport [103]. Thus, putative bacteriocins can be identified by comparing new genome sequences against well-characterized biosynthetic genes or gene clusters. This “genome mining” approach allows for the discovery of potentially novel bacteriocins in a complete culture-independent fashion, with the potential to reduce the rediscovery rate of known molecules [104]. Various powerful tools with broad databases have been created for the automated screening of bacteriocin gene clusters. BAGEL4 (http://bagel4.molgenrug.nl/) (accessed on 15 January 2022) is a versatile fast genome-mining tool valid for modified- and non-modified bacteriocins [105]. BAGEL4 uses DNA nucleotide sequences as the input, which are analyzed in parallel via two different approaches; one is the context of bacteriocin- or RiPP (ribosomally synthesized and post-translationally modified peptides) gene-based mining, the other is the precursor (structural gene)-based mining directly by Glimmer, which increases the success rate and lowers the need for the manual evaluation of results [105]. By genome mining of 1011 LAB strains (including WGS and complete genomes) of 82 species using BAGEL4, we shed light on the diversity of food-associated LAB that processes biosynthetic genes of class II bacteriocin at the species level (Table 3, Supplementary Table S1).

4.2. In Silico Prediction of the Distribution of Class II Bacteriocins in LAB

4.2.1. Carnobacteria

Carnobacteria are ubiquitous LAB occurring in different foods. Three sepicies, Carnobacterium piscicola, Carnobacterium divergens, and Carnobacterium maltaromaticum, have been frequently isolated from various meat and dairy products [106]. C. piscicola produces bacteriocins, namely piscicocin V1a and piscicocin V1b of molecular weights 4416 Da and 4526 D [107]. C. piscicola 213 produces carnocin KZ213 with strong antilisterial activity [108]. In C. maltaromaticum, 43.75% of investigated strains possess class IIa bacteiocins, which mainly include carnobacteriocin_BM1 and carnobacteriocin_B2 (Supplementary Table S1). A dry-formulated live culture of C. maltaromaticum CB1 which produces carnobacteriocin BM1 has been commercially used as a biopreservative against L. monocytogenes in meat [109].

4.2.2. Enterococci

The genus Enterococcus is the most controversial group of LAB that comprises both pathogenic and commensal microorganisms; some strains of Enterococcus spp. are highly adapted to several food systems, and they are also involved in the fermentation activity of traditionally manufactured cheese, dry sausages, and olives [110]. The production of bacteriocins by enterococci is well documented. Our analysis shows that Enterococcus faecium and E. faecalis are predominant species that producing class II bacteriocins, which is in accordance with previous reports [111]. E. durans and E. mundtii also have great potential for class II bacteriocin screening. More than 50% of investigated strains have at least one bacteriocin encoding genes (Table 3).

4.2.3. Lactobacilli Group

The genus Lactobacillus used to comprise over 200 species, making it the largest and most diverse genus of LAB [112]. In 2020, a taxonomic reorganization of the lactic acid bacteria reclassified the genus Lactobacillus into 25 genera. The lactobacilli group occupies a variety of niches, including milk and plant surfaces, as well as the gastrointestinal tract of humans and animals [113]. Lactobacillus spp. has been deployed and studied extensively as fermentation starter cultures and as probiotics, of which bacteriocin production has been considered an important trait. However, the ability to produce class II bacteriocins varied among different species. Notably, almost all L. acidophilus strains contain IIa, IIb and IId bacteriocins. L. casei, L. paracasei and L. rhamnosus stand out as rich sources of IIa and IId bacteriocin.

4.2.4. Lactococci

Due to their particular ability to ferment lactose, members of the genus Lactococcus are widely used as starter cultures in the dairy industry. Some strains of lactococci of human and milk origin are reported to have probiotic properties [114]. This genus is well known for its ability to produce class I bacteriocin nisin. Our analysis showed that some species also have considerable potential for class II bacteriocin. Specifically, 85% of tested Lc. lactis subsp. cremoris strains and 50% of tested Lc. lactis subsp. lactis strains harbor class IId bacteriocin. Class IIa and IId bacteriocins were found in some Lc. piscium and Lc. raffinolactis strains.

4.2.5. Leuconostoc Spp.

The genus Leuconostoc naturally exists in vegetables and some fermented dairy products [115]. Some species of this genus were considered major microorganisms responsible for food spoilage [116]. Class II bacteriocin genes were mainly detected in L. gelidum, L. lactis, and L. mesenteroides, of which the class IId was the dominant subgroup (Table 3). The genus Pediococcus has a negative role in the spoilage of beer/wine and a positive role in many fermented foods. Most species of this genus are used in the food industry as probiotic products and starter cultures for fermentation [117].

4.2.6. Pediococci

The genus Pediococcus consists of eight species and various species and strains differ in tolerance to oxygen, pH, temperature, and NaCl [118]. P. acidilactici and P. pentosaceus take place in food fermentations either as indigenous microflora or in starters, and both have been used in natural and controlled fermentations of vegetables and sausages. Studies have shown that non-starter and adjunct Pediococcus spp. impart desirable attributes to cheese [119]. P. pentosaceus, P. damnosus, and P. acidilactici are major species of this genus that are capable of producing class II bacteriocins, especially pediocin and other class IIa bacteriocins.

4.2.7. Others

Streptococcus thermophilus is the only streptococcal species widely used in food fermentations, especially for yogurt manufacturing [120]. Several S. thermophiles strains can produce thermophilin 13, a two-peptide class IIb bacteriocin. Most S. thermophiles strains contain genes encoding bacteriocin-like peptide (blp), which was also frequently detected in other pathogenic streptococci strains [121]. The genus Oenococcus plays an important role in wine fermentation, while the species Weissella have been described to be associated with vegetable fermentations [122]. However, no class II bacteriocin encoding genes were detected in these two genera.

5. Biosynthesis and Genetics

5.1. IIa

Class IIa bacteriocin is first ribosomally synthesized as a prebacteriocin, which contains an N-terminal leader sequence to keep the peptide inactive (Figure 1). The leaders contain 15 to 30 residues, most of which are featured for the double-glycine residues upstream of the cleavage site. The leader is believed to serve as a signal sequence for the processing and secretion of bacteriocins by a dedicated system comprising an ABC transporter and an accessory protein. ABC-transporter protein contains the C-terminal ATP-binding domain and the N-terminal transmembrane domain embedded in the membrane bilayer. The N-terminal region can cleave the leader peptide at the double-glycine motif. The binding of prebacteriocin with N-terminal proteolytic domain triggers the ATP hydrolysis and subsequent conformational changes of the transporter, resulting in leader cleavage and translocation of the mature bacteriocin across the membrane [14]. The accessory proteins are postulated to facilitate the membrane translocation and/or help in the processing of the leader peptide [14]. For some class IIa bacteriocins, the accessory protein ensures the formation of correct disulfide bond formation [123]. However, not all class IIa bacteriocins are transported via ABC-transporter. Some bacteriocins including enterocin P, bacteriocin 31, enterocin SE-K4 lack the double-glycine motif in their leaders and are exported by sec-dependent translocation system [20,29,124]. These bacteriocins have a hydrophobic N-terminal sec-dependent leader to direct the secretion of the prebacteriocins. The leader was removed by a signal peptidase during translocation.
The synthesis of class IIa bacteriocins is typically regulated by a quorum sensing (QS) system that consists of three components, an inducing peptide, a membrane-associated histidine protein kinase (HPK) and a cytoplasmic response regulator (RR). The inducing peptide is initially synthesized as a prepeptide with N-terminal leader sequence, which is cleaved upon secretion by the ABC-transporter. The concentration of inducer peptide increased along with cell growth. An excess in inducer peptide concentration activates the three-component system by triggering the autophosphorylation of HPK, which transfers a phosphate group to its cognate RR. The phosphorylated RR acts as a transcriptional activator and activates the expression of biosynthetic gene clusters (Figure 1). Moreover, environmental parameters may influence the production of class IIa bacteriocin by acting on the bacteriocin regulatory system or affecting the binding of the induction peptide to HPK [125].
The bacteriocin-producing bacteria avoid killing by their own bacteriocins through the co-expression of immunity proteins. Immunity proteins for the class IIa bacteriocins range from 81 to 115 amino acids in length and display substantial variation in their sequences. The C-terminal region is involved in specific recognition of their related bacteriocins. However, “cross-immunity” against other class IIa bacteriocins was observed [126]. The immunity protein folds into a globular protein in an aqueous solution and contains an antiparallel four-helix bundle [127]. There are currently two models being proposed regarding the mechanism of immunity protein: (i) the immunity protein directly interacts with the bacteriocin to obstruct pore formation; (ii) the immunity protein binds to the cytoplasmic side of the receptor and blocks the receptor’s ability to interact with the bacteriocin (Figure 1). Although direct evidence of contact between the immunity protein and bacteriocin has not been obtained, there are experimental data to support the first model. The expression of MunC protein (enterocin CRL35 immunity protein) in E. coli is sufficient to prevent the lethal effects of the hybrid suicide probe EtpM-enterocin CRL35. E. coli is naturally insensitive to enterocin CRL35, since it does not express the receptor. These results prove that the immunity protein MunC can protect bacterial cells in the absence of the receptor [27]. The second model of “indirect immunity protein and bacteriocin binding” was recently proved experimentally. When the bacterocin targets the membrane from the outside, it gets locked onto the receptor by its immunity protein by forming a ternary complex. For pediocin PA-1, both IIC and IID components of the man-PTS play an important role in the specific recognition between the bacteriocin-receptor complex and the immunity protein PedB [128].
Production of class IIa bacteriocins is often associated with the presence of a plasmid. In some cases, the biosynthetic gene clusters could be located in the chromosome, as exemplified by enteriocin A, divercin V41, sakacin P and canobacteriocin B2, etc. The genetic organization of this class shows considerable conservation. The gene cluster encoding class IIa bacteriocins usually also contain an operon that encodes ABC-transporters and their accessory proteins. The bacteriocin structural genes are generally located in a small operon with the immunity genes, with the exception of divercin V41, mundicin KS and mundicin L (Figure 2). For most class IIa bacteriocins, three genes encoding the regulatory system are located in the same operon, in which the two genes encoding HPK and RR follow the gene encoding the inducing peptide (Figure 2). Intriguingly, the sakacin G gene cluster contains duplicated structural genes skgA1 and skgA2 that encode essentially identical bacteriocin. The leader sequence of SkgA1 and SkgA2 differed only by three residues [39].

5.2. IIb

Similar to some class IIa bacteriocins, class IIb bacteriocins are initially synthesized as precursor peptides containing N-terminal extensions (leader peptides) which are cleaved off during maturation. All class IIb bacteriocins identified so far contain a double-glycine-type leader. The ATP-binding cassette (ABC) transporter and an accessory protein lead to the cleavage of inactive pre-peptide with the concomitant export of the mature bacteriocin across the cytoplasmic membrane. The accessory protein may be involved in immunity against the bacteriocin or required for secretion of the bacteriocin. However, for some two-peptide bacteriocins such as sakacin T, the processing and secretion are solely dependent on the ABC-transporter since the gene encoding the accessory protein is absent [129].
The production of class IIb bacteriocins was commonly regulated by a three-component regulatory system. The inducing peptide acts as an indicator of the cell density, which is sensed by the corresponding HK, resulting in the activation of the RR, which then activates the expression of all operons necessary for bacteriocin synthesis, transport, and regulation. The best example of such a regulatory system is the production of plantaricin E/F and plantaricin J/K by L. plantarum C11. The inducing peptide plantaricin A is secreted at low basal levels, thus enabling the bacterium to sense its own growth. At a certain threshold level of plantaricin A, an autoinduction loop is triggered, which leads to massive production of plantaricin E/F and plantaricin J/K [130]. Notably, there are two RRs encoded by L. plantarum C11, PlnC and PlnD. It has been shown that PlnC activates while PlnD represses the genes involved in bacteriocin synthesis [131] (Figure 3). However, truncated versions of the activator PlnC, resulting from the translation from alternative start codons within plnC, were found to exhibit repression on the bacteriocin biosynthesis operon [132]. Moreover, L. lactis MG1363 produced supernatants acting as environmental signals which can switch on bacteriocin production in L. plantarum NC8 via a quorum-sensing mechanism mediated by the inducing peptide PLNC8IF [133].
The mechanism of how immunity proteins protect producing cells from class IIb bacteriocins was not fully elucidated. Some immunity proteins, including plnI for plantaricin EF and plnLR for plantaricin JK, show homology to the Abi family of proteins, which are putative membrane-bound metalloproteases characterized by three conserved motifs. These immunity proteins probably function by proteolytically degrading their cognate bacteriocins [134]. Other immunity proteins, including the immunity protein for lactococcin G, likely interact directly both with the bacteriocin and its cellular receptor [135]. So far, all the immunity proteins for class IIb bacteriocins are predicted to contain transmembrane domains (TMD). However, they range in length, number of TMDs, and orientation across the membrane. The smallest immunity protein, CbnZ for carnobacteriocin XY, has just 42 amino acids and contains as few as one TMD, while LagC is a membrane-associated protein with four TMDs [136]. The wide structural variety of immunity proteins may be attributed to the fact that class IIb bacteriocins adopt different receptors as targeting molecules.
A typical gene set for class IIb bacteriocin production comprises five to eight genes (Figure 4) [137,138,139]. These include two bacteriocin encoding genes, whose closely adjacent gene encodes the immunity protein. The genes encoding a three-component regulatory system may locate up- or downstream of the bacteriocin structural genes. Most class IIb gene clusters also have two genes encoding an ABC transporter complex.

5.3. IIc

Three key steps are involved in the biosynthesis of circular bacteriocins: cleavage of the leader, circularization, and exportation of the mature bacteriocin. Leader cleavage is believed to be the first step in the maturation and a requirement for further processing into the mature bacteriocins. The leader peptides ranging between 2 and 35 amino acids share no sequence similarity and the function of the leaders awaits further investigation. Unlike class IIa and IIb bacteriocins, whose leader was generally cleaved at the double-glycine site, there is no common recognition site for leader cleavage of circular bacteriocins. Moreover, the enzymes responsible for the cleavage of the leader peptide have not yet been identified.
The exact mechanism of the circularization reaction for circular bacteriocins is not fully understood. The ligation sites of all circular bacteriocins are located within a helical structure, consisting mainly of stretches of hydrophobic residues. It was suggested that the hydrophobic environment is essential for the circularization reaction [16]. The properties of both the N- and C-terminal residues are critical to the efficiency of the circularization process. In the case of AS-48, the substitution of Met1 to Ala lowered the circularization efficiency significantly, whereas the substitution of Trp70 (last residue) to Ala resulted in the production of both circular and linear forms of the bacteriocin [140]. Mutational analysis at the Leu1 position of enterocin NKR-5-3B revealed that only mutations with helix structure-promoting hydrophobic residues (Ala, Ile, Val or Phe) were able to yield the mature Ent53B derivative [141]. These results highlight the importance of the hydrophobic nature of ligation points for the circularization mechanism. Most of the proteins encoded by the biosynthetic gene clusters contain multiple putative membrane-spanning domains and are probably associated with the membrane (Figure 5). The circularization reaction may be catalyzed by a membrane-located protein complex [142]. Such a complex may be also responsible for exporting circular bacteriocins in a manner of coupling circularization and secretion reactions.
Several proteins have been identified to be involved in immunity to circular bacteriocins. As-48D1, GaaI, and CclI are the dedicated immunity proteins for AS-48, gassericin A, and carnocyclin A, respectively [143,144,145]. These immunity proteins are small (49–56 amino acids), cationic (high pI), and contain one or two transmembrane domains, suggesting that they may be located in the cell membrane. These immunity proteins can provide a certain level of immunity to their cognate bacteriocins. Full immunity requires the combined activity of several other proteins.
Circular bacteriocin gene clusters often consist of overlapping genes, demonstrating a tight organizational structure or genes which depend upon the ribosomal binding site of upstream genes (Figure 5). This indicates that expression is regulated by translational coupling. The minimal set of genes required for bacteriocin production and immunity, in general, comprises 5 to 10 genes [146]. Interestingly, the bacteriocin structural genes are not adjacent to the immunity genes, some of them are located in different operons (Figure 5). The transportation system of class IIc bacteriocins is usually more complex than other class II bacteriocins. They have an accessory operon (cclEFGH, as-48EFGH, garEFGH) encoding an ABC transporter complex, consisting of a permease, an ATPase, and an extracellular protein (Figure 5).

5.4. IId

Most of the leaderless bacteriocins remain to be studied in more detail regarding the biosynthetic mechanism. The leader sequences of other general bacteriocins play an important role in the recognition by transporters. Moreover, the leader sequences keep the precursor peptides inactive during biosynthesis inside the host until the appropriate time for secretion. How leaderless bacteriocins are recognized by transporter protein and secreted remains elusive. A distinguishing feature of leaderless bacteriocins is the presence of a formylated N-terminal methionine residue. Interestingly, lacticins Q expressed in E. coli BL21(DE3) has unformylated methionine at the N-terminal. Nevertheless, the peptide demonstrated antimicrobial activity against several of the indicator strains tested [147]. Thus, leaderless bacteriocins may not require a formylated N-terminus for full activity. However, more studies are needed to decipher the importance of the formylated methionine at the N-terminus for the biosynthesis of leaderless bacteriocins. The leaderless bacteriocins are active immediately after their translation process. The transport and immunity of leaderless bacteriocins may be carried out by one protein or protein complex. LmrB, an ABC-type multidrug resistance transporter, has been shown to be involved in both the secretion and self-immunity of this leaderless bacteriocin [148]. The secretion of lacticin Q is strictly controlled by the presence of LnqBCDEF complex, whereas immunity is flexible in that LnqEF (ABC transporter) is the minimal unit required for sufficient immunity and LnqBCD could be considered an accessory protein that supports the activity of LnqEF [149]. This may indicate that leaderless bacteriocins have in common the feature of having one dedicated ABC transporter mediating both secretion and immunity. However, a recent study showed that the ABC transporter is only involved in the transport but not the immunity of enterocin DD14, a leaderless two-peptide bacteriocin. The intracellular enterocin DD14 plays a role in its own immunity system [150].
Similar to class IIa and IIb bacteriocins, the non-pediocin liner bacteriocins are synthesized as biologically inactive pre-peptides consisting of an N-terminal leader peptide. Following synthesis of the pre-peptide, cleavage of the N-terminal leader sequence generally occurs at the double glycine site by means of a dedicated membrane protein from the ATP-binding cassette transporter family. In addition, a number of non-pediocin liner bacteriocins including lactococcin 972 and divergicinA are secreted through a general sec-dependent pathway and their leaders are cleaved by extracellular signal peptidase. Most LAB have a dedicated immunity protein to protect the cells from their own non-pediocin liner bacteriocins. It is not clear if there is a common mechanism of immunity for non-pediocin liner bacteriocins. For Lactococcin A, its immunity protein LciA has a similar four-helix bundle fold with the immunity proteins of the pediocin-like bacteriocins. Interestingly, LciA and the pediocin-like immunity proteins function in a similar manner. They bind to the bacteriocin–man-PTS complex and prevent membrane leakage [151].
The gene clusters for most of the leaderless bacteriocins have been identified. Genes involved in transport and immunity are often closely associated with bacteriocin structural genes (Figure 6). Leader-containing bacteriocins need an accessory protein function together with the cognate ABC transporter to mediate bacteriocin secretion. Such an accessory protein is not required for transporting leaderless bacteriocins. Moreover, genes related to formylase synthesis were not found in the vicinity of the bacteriocin structural gene, indicating that the N-terminal formylation of leaderless bacteriocins may be carried out by a host-encoded formylase that exists outside of the biosynthetic gene cluster [16,152]. Interestingly, the structural genes of two leaderless bacteriocins weissellicin Y and weissellicin M produced by Weissella hellenica QU 13 are located in the same locus [87] (Figure 6). The structural genes of multi-peptides leaderless bacteriocins are co-transcribed. For instance, there is only one promoter has been detected upstream of the ddA gene, and a clear processing site motif of 48 bp was detected between the ddB and ddC genes [150]. The genes responsible for regulation were only found in the biosynthetic gene cluster of lacticinQ/Z, whose production was positively regulated by LnqR, a TetR-family transcriptional regulator [153] (Figure 6).
The regulation of most leaderless bacteriocins was associated with environmental stimuli. The production of Enterocin L50, Enterocin P, and Enterocin Q by Enterococcus faecium L50 was temperature-dependent [154]. The production of weissellicin Y and weissellicin M by Weissella hellenica QU 13 was nutrition-adaptive and thiamine addition decreases weissellicin Y production [155]. Pasteurized milk supplemented with tryptone significantly improved the production of garvicin KS [156].

6. Production of Class II Bacteriocins by Microbial Fermentation

The biosynthesis of bacteriocins can be influenced by various culture conditions, such as the composition of the medium, pH, temperature, and growth kinetics of the microorganisms [157]. Fermentation studies on the class II bacteriocin production indicate that it follows primary metabolite kinetics producing the bacteriocin during the growth phase and declines completely after entering the stationary phase [158]. The commercial availability of bacteriocins is still limited due to the low yield of the product. Moreover, bacteriocin-producing LAB needs complex nutrition to grow, and this not only increases the production cost but also gives rise to the difficulties related to their purification. The efficient use of these compounds requires various approaches to overcome the low yield and the high production costs. In this regard, different studies have examined the effects of various media compositions and culture conditions on the yield of bacteriocins [159]. In recent years, growing knowledge of the genetics and biosynthesis of class II bacteriocins has enabled researchers to quickly manufacture and engineer LAB strains for improved bacteriocin production. LAB strains developed by genetic engineering can not only be used to enhance yields but also for increased tolerance to various biotic and abiotic stresses during fermentation.

6.1. Natural Fermentation

Various media are used to cultivate the bacteriocin-producer such as CM, SM8, M17, and MRS media. These media are good for neutralizing lactic acid and improving cell growth, but do not consider the accumulation of bacteriocin and high content of nitrogen sources, especially proteins and peptides, that may bring about the difficulties of bacteriocin purification [160]. Avonts et al. compared the bacteriocin production of seven Lactobacillus strains during fermentation in MRS medium and milk medium [161]. Their results showed that L. acidophilus IBB 801 and L. gasseri K7 performed better than L. casei complex strains including L. rhamnosus GG. Although natural fermentation only reached a limited bacteriocin yield, the preservation potential of bacteriocins could be achieved by applying a bacteriocin-producing strain as starter culture.
Most class II bacteriocins are regulated by a quorum sensing (QS) system whose initiation can be induced by environmental factors and other bacterial strains. The production of class IIb bacteriocin plantaricin NC8 by L. plantarum NC8 is inducible by co-culture with Gram-positive bacterial strains and requires cell-to-cell contact with the inducer bacteria [61]. This activates the expression of the operon plNC8IF-plNC8HK-plnD encoding a three-component regulatory system (TCRS) formed by an autoinducer peptide (PLNC8IF), a histidine protein kinase (PLNC8HK), and a response regulator (PlnD), which is indispensable for bacteriocin production by NC8 and is thought to be involved in quorum sensing [162]. The bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation has a close relationship with LuxS-mediated quorum sensing system [163]. Enhanced bacteriocin production in a co-culture system has also been reported in Pediococcus pentosaceus and Enterococcus faecium [164,165].

6.2. Improving Class II Bacteriocin Production by Optimizing Fermentation Conditions

Similar to other metabolites, the yield of class II bacteriocins was strongly influenced by medium compositions and fermentation factors. The optimization of fermentation conditions is a complex approach but critically essential for high-performance bacteriocin production at a commercial scale [158]. The culture medium is one of the key factors that need to be considered in the enhancement of any fermentation processes. The properties of the growth media including amino acid composition, carbon/nitrogen ratio, pH and lactose levels have a great influence on the change in biomass of the culture and the corresponding change in the level of bacteriocin production. In many cases, the optimal growth medium does not reflect the optimal productivity of bacteriocins by strain producers. The production of bacteriocins by L. lactis Gh1 in soytone was 1.28-times higher as compared to that of organic nitrogen sources ((NH4)2SO4) [166]. The addition of certain amino acids in the fermentation medium stimulates bacteriocin production. For instance, glycine and cystine could stimulate the production of certain bacteriocins, while no stimulus effect was observed for alanine, tyrosine, and glutamic acid [167].
It was reported that some stressful environments could enhance bacteriocin production. For instance, a downward temperature shift stimulated amylovorin L471 production [168]. Nutrient stress is known to increase the bacteriocin production capability of L. plantarum B21 during industrial processing. Further investigation revealed that unstressed L. plantarum B21 cells use glucose as their primary energy source with high concentrations of metabolites involved in glycolysis and organic acid synthesis. In contrast, large numbers of metabolites involved in amino acid metabolism were upregulated in glucose-stressed cells, indicating that they were using amino acids as their main source of energy, which may favor the synthesis of bacteriocin [169]. The effects of NaCl on bacteriocin production are controversial. It has been reported that the supplementation of appropriate NaCl could enhance the growth and bacteriocin production of Lactobacillus amylovorus DCE 471 [170], while optimum bacteriocin production by L. plantarum 17.2b requires the absence of NaCl [168]. Other inorganic ions including KH2PO4, CaCl2 and NH4PO4 also have a profound influence on bacteriocin production [171].
Given the high number of influencing factors, the application of an adequate experimental design (optimization) is the best strategy to obtain maximum information with a minimum number of experiments. Response surface methodology is a powerful tool used for building models and evaluating the effects of factors and searching for optimum conditions of factors for bacteriocin production [172]. For Latilactobacillus curvatus P99, RSM analysis revealed that the optimum production of bacteriocin was obtained at pH 6.22 and 30.6 °C for 17.9 h. Suganthi and Mohanasrinivasan reported a 20-fold increase in bacteriocin for Pediococcus pentosaceus KC692718 by using the RMS tool. The optimum conditions were soytone (1.03%), sucrose (2.4%), pH (5.5) and temperature (34.5 °C) [173].

6.3. Improving Class II Bacteriocin Production by Genetic Engineering

Besides the optimization of fermentation conditions, bacteriocin production can be increased by genetic approaches either by engineering the producer cells or using various heterologous expression systems. The entire gak locus including the genes involved in immunity and transport of class IId bacteriocin garvicin KS was cloned into a plasmid and transformed into native producers Lactococcus garvieae KS1546. The bacteriocin of the engineered KS1546 in optimized medium is about 2000-fold higher compared to that initially achieved by wild-type strain in GM17 [156]. A green fluorescent protein (gfp)-based promoter-trap reporter system was used to screen conditions with enhanced bacteriocin production by Companilactobacillus crustorum MN047 [174].
Recombinant bacteriocin production was also widely investigated by using bacteria and yeast cells as hosts. Heterologous expression of three different class II bacteriocins, sakacin P, pediocin PA-1 and piscicolin 61, was successful in L. sake Lb790 (pSAK20). Bacteriocin enterocin A and its immune protein Ent I from E. faecium T136 were cloned for co-expression under Lc. lactis MG1363 Usp45 protein signal peptide [175]. Arbulu et al. reported the use of synthetic genes designed from the published amino acid sequence of the mature bacteriocins SRCAM 602, OR-7, E-760, and L-1077 and with adapted codon usage for successful expression by Pichia pastoris [176]. The class IIb two-peptide bacteriocins plantaricin EF (composed of PlnE and PlnF) and plantaricin NC8 (composed of PLNC8α and PLNC8β) were successfully heterologously expressed in E. coli BL21 cells to enhance bacteriocin production yield [177]. Yu et al. constructed recombinant plasmids harboring genes encoding bacteriocin lactocinAB and expressed in E. coli BL21 cells with high yield [178]. The enterocin P signal peptide was used to facilitate the secretion of the munA-cvaC hybrid bacteriocin in Lc. lactis NZ9000. The engineered hybrid bacteriocin was produced in situ in food products to effectively control Gram-negative and Gram-positive foodborne pathogens [179].

7. Conclusions

Class II bacteriocins of LAB with broad-spectrum antibacterial activity are expected to play a major role in many fields. Bacteriocins have great potential for use as biopreservatives, antibiotic alternatives, health-promoting gut modulators, and animal growth promoters [180]. Class II bacteriocins can be directly applied as food preservatives. Moreover, some bacteriocins, e.g., AS-48, become alternative antibiotics through the development of bacteriocin-based therapies and offer promising revenue to address the problem of antibiotic resistance.
In general, LAB strains have a system to coordinate the production of class IIa and IIb bacteriocins at an adequate stage of growth, which is called a quorum-sensing system. The regulation mechanisms of the genes encoding class IIc and IId bacteriocin biosynthesis need to be investigated further. The potential application of bacteriocin as natural food preservatives depends on the capacity of expression of bacteriocin genetic determinants by genetically modified heterologous host strains at the industrial level. At present, commercial-scale bacteriocin production is still hampered by high costs and low yield. Overcoming this task will be unimaginable without a deep understanding of the bacteriocins’ genetics and biosynthesis. In the last few decades, our understanding of bacteriocins’ biosynthesis and regulation has considerably increased, which provides opportunities for the development of more advanced systems for the cost-effective production of bacteriocins.

Supplementary Materials

The following supporting information can be downloaded at https://0-www-mdpi-com.brum.beds.ac.uk/article/10.3390/fermentation8050217/s1: Table S1: Genome mining of class II bacteriocins of food-associated lactic acid bacterial strains.

Author Contributions

Conceptualization, T.Z., Y.Z., L.L. and F.Z.; writing—original draft preparation, T.Z., Y.Z., X.J., Z.C. and Y.Y.; writing—review and editing, L.L. and F.Z.; supervision, Y.Y.; funding acquisition, F.Z. and Y.Y. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (No. 31901667) and Natural Science Basic Research Program of Shaanxi (No. 2021JQ-138).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Ruiz Rodríguez, L.G.; Mohamed, F.; Bleckwedel, J.; Medina, R.; De Vuyst, L.; Hebert, E.M.; Mozzi, F. Diversity and functional properties of lactic acid bacteria isolated from wild fruits and flowers present in Northern Argentina. Front. Microbiol. 2019, 10, 1091. [Google Scholar] [CrossRef] [PubMed]
  2. Dai, M.; Li, Y.; Xu, L.; Wu, D.; Zhou, Q.; Li, P.; Gu, Q. A novel bacteriocin from Lactobacillus pentosus ZFM94 and its antibacterial mode of action. Front. Nutr. 2021, 8, 710862. [Google Scholar] [CrossRef] [PubMed]
  3. Umu, Ö.C.; Bäuerl, C.; Oostindjer, M.; Pope, P.B.; Hernandez, P.E.; Perez-Martinez, G.; Diep, D.B. The potential of class II bacteriocins to modify gut microbiota to improve host health. PLoS ONE 2016, 11, e0164036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Yount, N.Y.; Weaver, D.C.; de Anda, J.; Lee, E.Y.; Lee, M.W.; Wong, G.C.L.; Yeaman, M.R. Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm. Front. Immunol. 2020, 11, 1873. [Google Scholar] [CrossRef]
  5. Ishibashi, N.; Himeno, K.; Masuda, Y.; Perez, R.H.; Iwatani, S.; Zendo, T.; Wilaipun, P.; Leelawatcharamas, V.; Nakayama, J.; Sonomoto, K.J.A.; et al. Gene cluster responsible for secretion of and immunity to multiple bacteriocins, the NKR-5-3 enterocins. Appl. Environ. Microbiol. 2014, 80, 6647–6655. [Google Scholar] [CrossRef] [Green Version]
  6. Klaenhammer, T.R. Genetics of bacteriocins produced by lactic acid bacteria. FEMS Microbiol. Rev. 1993, 12, 39–85. [Google Scholar] [CrossRef]
  7. Cotter, P.D.; Hill, C.; Ross, R.P. Bacteriocins: Developing innate immunity for food. Nat. Rev. Microbiol. 2005, 3, 777–788. [Google Scholar] [CrossRef]
  8. Alvarez-Sieiro, P.; Montalban-Lopez, M.; Mu, D.; Kuipers, O.P. Bacteriocins of lactic acid bacteria: Extending the family. Appl. Microbiol. Biotechnol. 2016, 100, 2939–2951. [Google Scholar] [CrossRef] [Green Version]
  9. Heng, N.C.; Wescombe, P.A.; Burton, J.P.; Jack, R.W.; Tagg, J.R. The diversity of bacteriocins in Gram-positive bacteria. In Bacteriocins: Ecology and Evolution; Riley, M.A., Chavan, M.A., Eds.; Springer: Berlin/Heidelberg, Gertmany, 2007; pp. 45–92. [Google Scholar]
  10. Heng, N.C.K.; Tagg, J.R. What’s in a name? Class distinction for bacteriocins. Nat. Rev. Microbiol. 2006, 4, 160. [Google Scholar] [CrossRef]
  11. Willey, J.M.; van der Donk, W.A. Lantibiotics: Peptides of diverse structure and function. Annu. Rev. Microbiol. 2007, 61, 477–501. [Google Scholar] [CrossRef]
  12. Sandiford, S.K. An overview of lantibiotic biosynthetic machinery promiscuity and its impact on antimicrobial discovery. Expert Opin. Drug Discov. 2020, 15, 373–382. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. McAuliffe, O.; Ross, R.P.; Hill, C. Lantibiotics: Structure, biosynthesis and mode of action. FEMS Microbiol. Rev. 2001, 25, 285–308. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Ennahar, S.; Sashihara, T.; Sonomoto, K.; Ishizaki, A. Class IIa bacteriocins: Biosynthesis, structure and activity. FEMS Microbiol. Rev. 2000, 24, 85–106. [Google Scholar] [PubMed]
  15. Nissen-Meyer, J.; Oppegård, C.; Rogne, P.; Haugen, H.S.; Kristiansen, P.E. Structure and mode-of-action of the two-peptide (class-IIb) bacteriocins. Probiotics Antimicrob. Proteins 2010, 2, 52–60. [Google Scholar] [CrossRef] [Green Version]
  16. Perez, R.H.; Zendo, T.; Sonomoto, K. Circular and Leaderless Bacteriocins: Biosynthesis, Mode of Action, Applications, and Prospects. Front. Microbiol. 2018, 9, 2085. [Google Scholar] [CrossRef]
  17. Iwatani, S.; Zendo, T.; Sonomoto, K. Class IId or linear and non-pediocin-like bacteriocins. In Prokaryotic Antimicrobial Peptides; Springer: Berlin/Heidelberg, Gertmany, 2011; pp. 237–252. [Google Scholar]
  18. Yi, Y.; Li, P.; Zhao, F.; Zhang, T.; Shan, Y.; Wang, X.; Liu, B.; Chen, Y.; Zhao, X.; Lü, X. Current status and potentiality of class II bacteriocins from lactic acid bacteria: Structure, mode of action and applications in the food industry. Trends Food Sci. Technol. 2022, 120, 387–401. [Google Scholar] [CrossRef]
  19. Kanatani, K.; Oshimura, M.; Sano, K. Isolation and characterization of acidocin A and cloning of the bacteriocin gene from Lactobacillus acidophilus. Appl. Environ. Microbiol. 1995, 61, 1061–1067. [Google Scholar]
  20. Tomita, H.; Fujimoto, S.; Tanimoto, K.; Ike, Y. Cloning and genetic organization of the bacteriocin 31 determinant encoded on the Enterococcus faecalis pheromone-responsive conjugative plasmid pYI17. J. Bacteriol. 1996, 178, 3585–3593. [Google Scholar] [CrossRef] [Green Version]
  21. Quadri, L.; Sailer, M.; Roy, K.L.; Vederas, J.C.; Stiles, M.E. Chemical and genetic characterization of bacteriocins produced by Carnobacterium piscicola LV17B. J. Biol. Chem. 1994, 269, 12204–12211. [Google Scholar] [CrossRef]
  22. De Kwaadsteniet, M.; Fraser, T.; Van Reenen, C.; Dicks, L. Bacteriocin T8, a novel class IIa sec-dependent bacteriocin produced by Enterococcus faecium T8, isolated from vaginal secretions of children infected with human immunodeficiency virus. Appl. Environ. Microbiol. 2006, 72, 4761–4766. [Google Scholar] [CrossRef] [Green Version]
  23. Quadri, L.; Sailer, M.; Terebiznik, M.R.; Roy, K.L.; Vederas, J.C.; Stiles, M.E. Characterization of the protein conferring immunity to the antimicrobial peptide carnobacteriocin B2 and expression of carnobacteriocins B2 and BM1. J. Bacteriol. 1995, 177, 1144–1151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Tichaczek, P.S.; Nissen-Meyer, J.; Nes, I.F.; Vogel, R.F.; Hammes, W.P. Characterization of the bacteriocins curvacin A from Lactobacillus curvatus LTH1174 and sakacin P from L. sake LTH673. Syst. Appl. Microbiol. 1992, 15, 460–468. [Google Scholar] [CrossRef]
  25. Metivier, A.; Pilet, M.-F.; Dousset, X.; Sorokine, O.; Anglade, P.; Zagorec, M.; Piard, J.-C.; Marlon, D.; Cenatiempo, Y.; Fremaux, C. Divercin V41, a new bacteriocin with two disulphide bonds produced by Carnobacterium divergens V41: Primary structure and genomic organization. Microbiology 1998, 144, 2837–2844. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Aymerich, T.; Holo, H.; Håvarstein, L.S.; Hugas, M.; Garriga, M.; Nes, I.F. Biochemical and genetic characterization of enterocin A from Enterococcus faecium, a new antilisterial bacteriocin in the pediocin family of bacteriocins. Appl. Environ. Microbiol. 1996, 62, 1676–1682. [Google Scholar] [CrossRef] [Green Version]
  27. Barraza, D.E.; Ríos Colombo, N.S.; Galván, A.E.; Acuña, L.; Minahk, C.J.; Bellomio, A.; Chalón, M.C. New insights into enterocin CRL35: Mechanism of action and immunity revealed by heterologous expression in Escherichia coli. Mol. Microbiol. 2017, 105, 922–933. [Google Scholar] [CrossRef] [Green Version]
  28. Arbulu, S.; Lohans, C.T.; van Belkum, M.J.; Cintas, L.M.; Herranz, C.; Vederas, J.C.; Hernandez, P.E. Solution structure of enterocin HF, an antilisterial bacteriocin produced by Enterococcus faecium M3K31. J. Agric. Food Chem. 2015, 63, 10689–10695. [Google Scholar] [CrossRef]
  29. Cintas, L.M.; Casaus, P.; Håvarstein, L.S.; Hernandez, P.E.; Nes, I.F. Biochemical and genetic characterization of enterocin P, a novel sec-dependent bacteriocin from Enterococcus faecium P13 with a broad antimicrobial spectrum. Appl. Environ. Microbiol. 1997, 63, 4321–4330. [Google Scholar] [CrossRef] [Green Version]
  30. Eguchi, T.; Kaminaka, K.; Shima, J.; Kawamoto, S.; Mori, K.; Choi, S.H.; Doi, K.; Ohmomo, S.; Ogata, S. Isolation and characterization of Enterocin SE-K4 produced by thermophilic enterococci, Enterococcus faecalis K-4. Biosci. Biotechnol. Biochem. 2001, 65, 247–253. [Google Scholar] [CrossRef]
  31. van Belkum, M.J.; Stiles, M.E. Molecular characterization of genes involved in the production of the bacteriocin leucocin A from Leuconostoc gelidum. Appl. Environ. Microbiol. 1995, 61, 3573–3579. [Google Scholar] [CrossRef] [Green Version]
  32. Héchard, Y.; Dérijard, B.; Letellier, F.; Cenatiempo, Y. Characterization and purification of mesentericin Y105, an anti-Listeria bacteriocin from Leuconostoc mesenteroides. Microbiology 1992, 138, 2725–2731. [Google Scholar] [CrossRef] [Green Version]
  33. Kawamoto, S.; Shima, J.; Sato, R.; Eguchi, T.; Ohmomo, S.; Shibato, J.; Horikoshi, N.; Takeshita, K.; Sameshima, T. Biochemical and genetic characterization of mundticin KS, an antilisterial peptide produced by Enterococcus mundtii NFRI 7393. Appl. Environ. Microbiol. 2002, 68, 3830–3840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Henderson, J.T.; Chopko, A.L.; Van Wassenaar, P.D. Purification and primary structure of pediocin PA-1 produced by Pediococcus acidilactici PAC-1.0. Arch. Biochem. Biophys. 1992, 295, 5–12. [Google Scholar] [CrossRef]
  35. Jack, R.W.; Wan, J.; Gordon, J.; Harmark, K.; Davidson, B.E.; Hillier, A.J.; Wettenhall, R.; Hickey, M.W.; Coventry, M.J. Characterization of the chemical and antimicrobial properties of piscicolin 126, a bacteriocin produced by Carnobacterium piscicola JG126. Appl. Environ. Microbiol. 1996, 62, 2897–2903. [Google Scholar] [PubMed]
  36. Reenen, V. Isolation, purification and partial characterization of plantaricin 423, a bacteriocin produced by Lactobacillus plantarum. J. Appl. Microbiol. 1998, 84, 1131–1137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Holck, A.; Axelsson, L.; Birkeland, S.-E.; Aukrust, T.; Blom, H. Purification and amino acid sequence of sakacin A, a bacteriocin from Lactobacillus sake Lb706. Microbiology 1992, 138, 2715–2720. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  38. Tichaczek, P.S.; Vogel, R.F.; Hammes, W.P. Cloning and sequencing of sakP encoding sakacin P, the bacteriocin produced by Lactobacillus sake LTH 673. Microbiology 1994, 140, 361–367. [Google Scholar] [CrossRef] [Green Version]
  39. Simon, L.; Fremaux, C.; Cenatiempo, Y.; Berjeaud, J. Sakacin G, a new type of antilisterial bacteriocin. Appl. Environ. Microbiol. 2002, 68, 6416–6420. [Google Scholar] [CrossRef] [Green Version]
  40. Svetoch, E.A.; Eruslanov, B.V.; Levchuk, V.P.; Perelygin, V.V.; Mitsevich, E.V.; Mitsevich, I.P.; Stepanshin, J.; Dyatlov, I.; Seal, B.S.; Stern, N.J. Isolation of Lactobacillus salivarius 1077 (NRRL B-50053) and characterization of its bacteriocin, including the antimicrobial activity spectrum. Appl. Environ. Microbiol. 2011, 77, 2749–2754. [Google Scholar] [CrossRef] [Green Version]
  41. Kaiser, A.L.; Montville, T.J. Purification of the bacteriocin bavaricin MN and characterization of its mode of action against Listeria monocytogenes Scott A cells and lipid vesicles. Appl. Environ. Microbiol. 1996, 62, 4529–4535. [Google Scholar] [CrossRef] [Green Version]
  42. Larsen, A.G.; Vogensen, F.; Josephsen, J. Antimicrobial activity of lactic acid bacteria isolated from sour doughs: Purification and characterization of bavaricin A, a bacteriocin produced by Lactobacillus bavaricus MI401. J. Appl. Bacteriol. 1993, 75, 113–122. [Google Scholar] [CrossRef]
  43. Yildirim, Z.; Winters, D.; Johnson, M. Purification, amino acid sequence and mode of action of bifidocin B produced by Bifidobacterium bifidum NCFB 1454. J. Appl. Microbiol. 1999, 86, 45–54. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Ferchichi, M.; Frère, J.; Mabrouk, K.; Manai, M. Lactococcin MMFII, a novel class IIa bacteriocin produced by Lactococcus lactis MMFII, isolated from a Tunisian dairy product. FEMS Microbiol. Lett. 2001, 205, 49–55. [Google Scholar] [CrossRef] [PubMed]
  45. Fimland, G.; Sletten, K.; Nissen-Meyer, J. The complete amino acid sequence of the pediocin-like antimicrobial peptide leucocin C. Biochem. Biophys. Res. Commun. 2002, 295, 826–827. [Google Scholar] [CrossRef]
  46. Bhugaloo-Vial, P.; Dousset, X.; Metivier, A.; Sorokine, O.; Anglade, P.; Boyaval, P.; Marion, D. Purification and amino acid sequences of piscicocins V1a and V1b, two class IIa bacteriocins secreted by Carnobacterium piscicola V1 that display significantly different levels of specific inhibitory activity. Appl. Environ. Microbiol. 1996, 62, 4410–4416. [Google Scholar] [CrossRef] [Green Version]
  47. Atrih, A.; Rekhif, N.; Moir, A.; Lebrihi, A.; Lefebvre, G. Mode of action, purification and amino acid sequence of plantaricin C19, an anti-Listeria bacteriocin produced by Lactobacillus plantarum C19. Int. J. Food Microbiol. 2001, 68, 93–104. [Google Scholar] [CrossRef]
  48. Wang, Y.; Qin, Y.; Xie, Q.; Zhang, Y.; Hu, J.; Li, P. Purification and characterization of plantaricin LPL-1, a novel class IIa bacteriocin produced by Lactobacillus plantarum LPL-1 isolated from fermented fish. Front. Microbiol. 2018, 9, 2276. [Google Scholar] [CrossRef]
  49. Flynn, S.; Van Sinderen, D.; Thornton, G.M.; Holo, H.; Nes, I.F.; Collins, J.K. Characterization of the genetic locus responsible for the production of ABP-118, a novel bacteriocin produced by the probiotic bacterium Lactobacillus salivarius subsp. salivarius UCC118 The GenBank accession number for the sequence reported in this paper is AF408405. Microbiology 2002, 148, 973–984. [Google Scholar]
  50. Neysens, P.; De Vuyst, L. Carbon dioxide stimulates the production of amylovorin L by Lactobacillus amylovorus DCE 471, while enhanced aeration causes biphasic kinetics of growth and bacteriocin production. Int. J. Food Microbiol. 2005, 105, 191–202. [Google Scholar] [CrossRef]
  51. Majhenič, A.Č.; Venema, K.; Allison, G.; Matijašić, B.B.; Rogelj, I.; Klaenhammer, T. DNA analysis of the genes encoding acidocin LF221 A and acidocin LF221 B, two bacteriocins produced by Lactobacillus gasseri LF221. Appl. Microbiol. Biotechnol. 2004, 63, 705–714. [Google Scholar] [CrossRef]
  52. Noda, M.; Miyauchi, R.; Danshiitsoodol, N.; Matoba, Y.; Kumagai, T.; Sugiyama, M. Expression of genes involved in bacteriocin production and self-resistance in Lactobacillus brevis 174A is mediated by two regulatory proteins. Appl. Environ. Microbiol. 2018, 84, e02707–e02717. [Google Scholar] [CrossRef] [Green Version]
  53. Acedo, J.Z.; Towle, K.M.; Lohans, C.T.; Miskolzie, M.; McKay, R.T.; Doerksen, T.A.; Vederas, J.C.; Martin-Visscher, L.A. Identification and three-dimensional structure of carnobacteriocin XY, a class IIb bacteriocin produced by Carnobacteria. FEBS Lett. 2017, 591, 1349–1359. [Google Scholar] [CrossRef] [PubMed]
  54. Hu, C.-B.; Malaphan, W.; Zendo, T.; Nakayama, J.; Sonomoto, K. Enterocin X, a novel two-peptide bacteriocin from Enterococcus faecium KU-B5, has an antibacterial spectrum entirely different from those of its component peptides. Appl. Environ. Microbiol. 2010, 76, 4542–4545. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Franz, C.M.; Grube, A.; Herrmann, A.; Abriouel, H.; Stärke, J.; Lombardi, A.; Tauscher, B.; Holzapfel, W.H. Biochemical and genetic characterization of the two-peptide bacteriocin enterocin 1071 produced by Enterococcus faecalis FAIR-E 309. Appl. Environ. Microbiol. 2002, 68, 2550–2554. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Kasuga, G.; Tanaka, M.; Harada, Y.; Nagashima, H.; Yamato, T.; Wakimoto, A.; Arakawa, K.; Kawai, Y.; Kok, J.; Masuda, T. Homologous expression and characterization of gassericin T and gassericin S, a novel class IIb bacteriocin produced by Lactobacillus gasseri LA327. Appl. Environ. Microbiol. 2019, 85, e02815–e02818. [Google Scholar] [CrossRef] [Green Version]
  57. Qi, F.; Chen, P.; Caufield, P.W. The group I strain of Streptococcus mutans, UA140, produces both the lantibiotic mutacin I and a nonlantibiotic bacteriocin, mutacin IV. Appl. Environ. Microbiol. 2001, 67, 15–21. [Google Scholar] [CrossRef] [Green Version]
  58. Moll, G.; Ubbink-Kok, T.; Hildeng-Hauge, H.; Nissen-Meyer, J.; Nes, I.F.; Konings, W.N.; Driessen, A. Lactococcin G is a potassium ion-conducting, two-component bacteriocin. J. Bacteriol. 1996, 178, 600–605. [Google Scholar] [CrossRef] [Green Version]
  59. Zendo, T.; Koga, S.; Shigeri, Y.; Nakayama, J.; Sonomoto, K. Lactococcin Q, a novel two-peptide bacteriocin produced by Lactococcus lactis QU 4. Appl. Environ. Microbiol. 2006, 72, 3383–3389. [Google Scholar] [CrossRef] [Green Version]
  60. Castellano, P.; Farias, M.E.; Holzapfel, W.; Vignolo, G. Sensitivity variations of Listeria strains to the bacteriocins, lactocin 705, enterocin CRL35 and nisin. Biotechnol. Lett. 2001, 23, 605–608. [Google Scholar] [CrossRef]
  61. Maldonado, A.; Ruiz-Barba, J.L.; Jiménez-Díaz, R. Production of plantaricin NC8 by Lactobacillus plantarum NC8 is induced in the presence of different types of gram-positive bacteria. Arch. Microbiol. 2004, 181, 8–16. [Google Scholar] [CrossRef] [Green Version]
  62. Stephens, S.K.; Floriano, B.; Cathcart, D.P.; Bayley, S.A.; Witt, V.F.; Jiménez-Díaz, R.; Warner, P.J.; Ruiz-Barba, J.L. Molecular analysis of the locus responsible for production of plantaricin S, a two-peptide bacteriocin produced by Lactobacillus plantarum LPCO10. Appl. Environ. Microbiol. 1998, 64, 1871–1877. [Google Scholar] [CrossRef] [Green Version]
  63. Ekblad, B.; Kyriakou, P.K.; Oppegård, C.; Nissen-Meyer, J.; Kaznessis, Y.N.; Kristiansen, P.E. Structure–function analysis of the two-peptide bacteriocin plantaricin EF. Biochemistry 2016, 55, 5106–5116. [Google Scholar] [CrossRef] [PubMed]
  64. Rogne, P.; Haugen, C.; Fimland, G.; Nissen-Meyer, J.; Kristiansen, P.E. Three-dimensional structure of the two-peptide bacteriocin plantaricin JK. Peptides 2009, 30, 1613–1621. [Google Scholar] [CrossRef] [PubMed]
  65. Barrett, E.; Hayes, M.; O’Connor, P.; Gardiner, G.; Fitzgerald, G.F.; Stanton, C.; Ross, R.P.; Hill, C. Salivaricin P, one of a family of two-component antilisterial bacteriocins produced by intestinal isolates of Lactobacillus salivarius. Appl. Environ. Microbiol. 2007, 73, 3719–3723. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Marciset, O.; Jeronimus-Stratingh, M.C.; Mollet, B.; Poolman, B. Thermophilin 13, a nontypical antilisterial poration complex bacteriocin, that functions without a receptor. J. Biol. Chem. 1997, 272, 14277–14284. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Kuo, Y.-C.; Liu, C.-F.; Lin, J.-F.; Li, A.-C.; Lo, T.-C.; Lin, T.-H. Characterization of putative class II bacteriocins identified from a non-bacteriocin-producing strain Lactobacillus casei ATCC 334. Appl. Environ. Microbiol. 2013, 97, 237–246. [Google Scholar] [CrossRef] [PubMed]
  68. Martin-Visscher, L.A.; van Belkum, M.J.; Garneau-Tsodikova, S.; Whittal, R.M.; Zheng, J.; McMullen, L.M.; Vederas, J.C. Isolation and characterization of carnocyclin A, a novel circular bacteriocin produced by Carnobacterium maltaromaticum UAL307. Appl. Environ. Microbiol. 2008, 74, 4756–4763. [Google Scholar] [CrossRef] [Green Version]
  69. Himeno, K.; Rosengren, K.J.; Inoue, T.; Perez, R.H.; Colgrave, M.L.; Lee, H.S.; Chan, L.Y.; Henriques, S.n.T.; Fujita, K.; Ishibashi, N. Identification, characterization, and three-dimensional structure of the novel circular bacteriocin, enterocin NKR-5-3B, from Enterococcus faecium. Biochemistry 2015, 54, 4863–4876. [Google Scholar] [CrossRef]
  70. Grande Burgos, M.J.; Pulido, R.P.; Del Carmen López Aguayo, M.; Gálvez, A.; Lucas, R. The cyclic antibacterial peptide enterocin AS-48: Isolation, mode of action, and possible food applications. Int. J. Mol. Sci. 2014, 15, 22706–22727. [Google Scholar] [CrossRef] [Green Version]
  71. Borrero, J.; Brede, D.A.; Skaugen, M.; Diep, D.B.; Herranz, C.; Nes, I.F.; Cintas, L.M.; Hernández, P.E. Characterization of garvicin ML, a novel circular bacteriocin produced by Lactococcus garvieae DCC43, isolated from mallard ducks (Anas platyrhynchos). Appl. Environ. Microbiol. 2011, 77, 369–373. [Google Scholar] [CrossRef] [Green Version]
  72. Masuda, Y.; Ono, H.; Kitagawa, H.; Ito, H.; Mu, F.; Sawa, N.; Zendo, T.; Sonomoto, K. Identification and characterization of leucocyclicin Q, a novel cyclic bacteriocin produced by Leuconostoc mesenteroides TK41401. Appl. Environ. Microbiol. 2011, 77, 8164–8170. [Google Scholar] [CrossRef] [Green Version]
  73. Sawa, N.; Zendo, T.; Kiyofuji, J.; Fujita, K.; Himeno, K.; Nakayama, J.; Sonomoto, K. Identification and characterization of lactocyclicin Q, a novel cyclic bacteriocin produced by Lactococcus sp. strain QU 12. Appl. Environ. Microbiol. 2009, 75, 1552–1558. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Borrero, J.; Kelly, E.; O’Connor, P.M.; Kelleher, P.; Scully, C.; Cotter, P.D.; Mahony, J.; van Sinderen, D. Plantaricyclin A, a novel circular bacteriocin produced by Lactobacillus plantarum NI326: Purification, characterization, and heterologous production. Appl. Environ. Microbiol. 2018, 84, e01801–e01817. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Golneshin, A.; Gor, M.-C.; Williamson, N.; Vezina, B.; Van, T.T.H.; May, B.K.; Smith, A.T. Discovery and characterisation of circular bacteriocin plantacyclin B21AG from Lactiplantibacillus plantarum B21. Heliyon 2020, 6, e04715. [Google Scholar] [CrossRef] [PubMed]
  76. Wirawan, R.E.; Swanson, K.M.; Kleffmann, T.; Jack, R.W.; Tagg, J.R. Uberolysin: A novel cyclic bacteriocin produced by Streptococcus uberis. Microbiology 2007, 153, 1619–1630. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  77. Acedo, J.Z.; van Belkum, M.J.; Lohans, C.T.; McKay, R.T.; Miskolzie, M.; Vederas, J.C. Solution structure of acidocin B, a circular bacteriocin produced by Lactobacillus acidophilus M46. Appl. Environ. Microbiol. 2015, 81, 2910–2918. [Google Scholar] [CrossRef] [Green Version]
  78. Kawai, Y.; Kemperman, R.; Kok, J.; Saito, T. The circular bacteriocins gassericin A and circularin A. Curr. Protein Pept. Sci. 2004, 5, 393–398. [Google Scholar] [CrossRef] [Green Version]
  79. Toba, T.; Samant, S.; Yoshioka, E.; Itoh, T. Reutericin 6, a new bacteriocin produced by Lactobacillus reuteri LA 6. Lett. Appl. Microbiol. 1991, 13, 281–286. [Google Scholar] [CrossRef]
  80. Liu, Y.-X.; Li, Z.-F.; Lv, Y.-J.; Dong, B.; Fan, Z.-C. Chlamydomonas reinhardtii-expressed multimer of Bacteriocin LS2 potently inhibits the growth of bacteria. Process Biochem. 2020, 95, 139–147. [Google Scholar] [CrossRef]
  81. Gálvez, A.; Valdivia, E.; Abriouel, H.; Camafeita, E.; Mendez, E.; Martínez-Bueno, M.; Maqueda, M. Isolation and characterization of enterocin EJ97, a bacteriocin produced by Enterococcus faecalis EJ97. Arch. Microbiol. 1998, 171, 59–65. [Google Scholar] [CrossRef]
  82. Criado, R.; Diep, D.B.; Aakra, A.; Gutiérrez, J.; Nes, I.F.; Hernández, P.E.; Cintas, L.M. Complete sequence of the enterocin Q-encoding plasmid pCIZ2 from the multiple bacteriocin producer Enterococcus faecium L50 and genetic characterization of enterocin Q production and immunity. Appl. Environ. Microbiol. 2006, 72, 6653–6666. [Google Scholar] [CrossRef] [Green Version]
  83. Uzelac, G.; Kojic, M.; Lozo, J.; Aleksandrzak-Piekarczyk, T.; Gabrielsen, C.; Kristensen, T.; Nes, I.F.; Diep, D.B.; Topisirovic, L. A Zn-dependent metallopeptidase is responsible for sensitivity to LsbB, a class II leaderless bacteriocin of Lactococcus lactis subsp. lactis BGMN1-5. J. Bacteriol. 2013, 195, 5614–5621. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Fujita, K.; Ichimasa, S.; Zendo, T.; Koga, S.; Yoneyama, F.; Nakayama, J.; Sonomoto, K. Structural analysis and characterization of lacticin Q, a novel bacteriocin belonging to a new family of unmodified bacteriocins of gram-positive bacteria. Appl. Environ. Microbiol. 2007, 73, 2871–2877. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Iwatani, S.; Zendo, T.; Yoneyama, F.; Nakayama, J.; Sonomoto, K. Characterization and structure analysis of a novel bacteriocin, lacticin Z, produced by Lactococcus lactis QU 14. Biosci. Biotechnol. Biochem. 2007, 71, 1984–1992. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  86. Lozo, J.; Mirkovic, N.; O’Connor, P.M.; Malesevic, M.; Miljkovic, M.; Polovic, N.; Jovcic, B.; Cotter, P.D.; Kojic, M. Lactolisterin BU, a novel class II broad-spectrum bacteriocin from Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4. Appl. Environ. Microbiol. 2017, 83, e01519-17. [Google Scholar]
  87. Masuda, Y.; Zendo, T.; Sawa, N.; Perez, R.; Nakayama, J.; Sonomoto, K. Characterization and identification of weissellicin Y and weissellicin M, novel bacteriocins produced by Weissella hellenica QU 13. J. Appl. Microbiol. 2012, 112, 99–108. [Google Scholar] [CrossRef]
  88. Cintas, L.M.; Casaus, P.; Herranz, C.; Håvarstein, L.S.; Holo, H.; Hernández, P.E.; Nes, I.F. Biochemical and genetic evidence that Enterococcus faecium L50 produces enterocins L50A and L50B, the sec-dependent enterocin P, and a novel bacteriocin secreted without an N-terminal extension termed enterocin Q. J. Bacteriol. 2000, 182, 6806–6814. [Google Scholar] [CrossRef] [Green Version]
  89. Martín-Platero, A.M.; Valdivia, E.; Ruíz-Rodríguez, M.; Soler, J.J.; Martín-Vivaldi, M.; Maqueda, M.; Martínez-Bueno, M. Characterization of antimicrobial substances produced by Enterococcus faecalis MRR 10-3, isolated from the uropygial gland of the hoopoe (Upupa epops). Appl. Environ. Microbiol. 2006, 72, 4245–4249. [Google Scholar] [CrossRef] [Green Version]
  90. Dubey, S.; Diep, D.B.; Evensen, Ø.; Munang’andu, H.M. Garvicin KS, a Broad-Spectrum Bacteriocin Protects Zebrafish Larvae against Lactococcus garvieae Infection. Int. J. Mol. Sci. 2022, 23, 2833. [Google Scholar] [CrossRef]
  91. Whitford, M.; McPherson, M.; Forster, R.; Teather, R. Identification of bacteriocin-like inhibitors from rumen Streptococcus spp. and isolation and characterization of bovicin 255. Appl. Environ. Microbiol. 2001, 67, 569–574. [Google Scholar] [CrossRef] [Green Version]
  92. Izquierdo, E.; Wagner, C.; Marchioni, E.; Aoude-Werner, D.; Ennahar, S. Enterocin 96, a novel class II bacteriocin produced by Enterococcus faecalis WHE 96, isolated from Munster cheese. Appl. Environ. Microbiol. 2009, 75, 4273–4276. [Google Scholar] [CrossRef] [Green Version]
  93. Tosukhowong, A.; Zendo, T.; Visessanguan, W.; Roytrakul, S.; Pumpuang, L.; Jaresitthikunchai, J.; Sonomoto, K. Garvieacin Q, a novel class II bacteriocin from Lactococcus garvieae BCC 43578. Appl. Environ. Microbiol. 2012, 78, 1619–1623. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Maldonado-Barragán, A.; Cárdenas, N.; Martínez, B.; Ruiz-Barba, J.L.; Fernández-Garayzábal, J.F.; Rodríguez, J.M.; Gibello, A. Garvicin A, a novel class IId bacteriocin from Lactococcus garvieae that inhibits septum formation in L. garvieae strains. Appl. Environ. Microbiol. 2013, 79, 4336–4346. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Martínez, B.; Rodríguez, A.; Suárez, J.E. Lactococcin 972, a bacteriocin that inhibits septum formation in lactococci. Microbiology 2000, 146, 949–955. [Google Scholar] [CrossRef] [Green Version]
  96. Holo, H.; Nilssen, Ø.; Nes, I. Lactococcin A, a new bacteriocin from Lactococcus lactis subsp. cremoris: Isolation and characterization of the protein and its gene. J. Bacteriol. 1991, 173, 3879–3887. [Google Scholar]
  97. Venema, K.; Abee, T.; Haandrikman, A.J.; Leenhouts, K.J.; Kok, J.; Konings, W.N.; Venema, G. Mode of action of lactococcin B, a thiol-activated bacteriocin from Lactococcus lactis. Appl. Environ. Microbiol. 1993, 59, 1041–1048. [Google Scholar] [CrossRef] [Green Version]
  98. Casaus, P.; Nilsen, T.; Cintas, L.M.; Nes, I.F.; Hernández, P.E.; Holo, H. Enterocin B, a new bacteriocin from Enterococcus faecium T136 which can act synergistically with enterocin A. Microbiology 1997, 143, 2287–2294. [Google Scholar] [CrossRef] [Green Version]
  99. Worobo, R.W.; Henkel, T.; Sailer, M.; Roy, K.L.; Vederas, J.C.; Stiles, M.E. Characteristics and genetic determinant of a hydrophobic peptide bacteriocin, carnobacteriocin A, produced by Carnobacterium piscicola LV17A. Microbiology 1994, 140, 517–526. [Google Scholar] [CrossRef] [Green Version]
  100. Nes, I.F.; Brede, D.A.; Diep, D.B. Chapter 16-Class II Non-Lantibiotic Bacteriocins. In Handbook of Biologically Active Peptides; Academic Press: Cambridge, MA, USA, 2013; pp. 85–92. [Google Scholar]
  101. Perez, R.H.; Zendo, T.; Sonomoto, K. Novel bacteriocins from lactic acid bacteria (LAB): Various structures and applications. Microb. Cell Factories 2014, 13, S3. [Google Scholar] [CrossRef] [Green Version]
  102. Nes, I.F.; Johnsborg, O. Exploration of antimicrobial potential in LAB by genomics. Curr. Opin. Biotechnol. 2004, 15, 100–104. [Google Scholar] [CrossRef]
  103. Aucher, W.; Lacombe, C.; Héquet, A.; Frère, J.; Berjeaud, J.-M. Influence of Amino Acid Substitutions in the Leader Peptide on Maturation and Secretion of Mesentericin Y105 by Leuconostoc mesenteroides. J. Bacteriol. 2005, 187, 2218–2223. [Google Scholar] [CrossRef] [Green Version]
  104. Letzel, A.-C.; Pidot, S.J.; Hertweck, C. Genome mining for ribosomally synthesized and post-translationally modified peptides (RiPPs) in anaerobic bacteria. BMC Genom. 2014, 15, 983. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  105. van Heel, A.J.; de Jong, A.; Song, C.; Viel, J.H.; Kok, J.; Kuipers, O.P. BAGEL4: A user-friendly web server to thoroughly mine RiPPs and bacteriocins. Nucleic Acids Res. 2018, 46, 278–281. [Google Scholar] [CrossRef] [PubMed]
  106. Casaburi, A.; Nasi, A.; Ferrocino, I.; Di Monaco, R.; Mauriello, G.; Villani, F.; Ercolini, D. Spoilage-related activity of Carnobacterium maltaromaticum strains in air-stored and vacuum-packed meat. Appl. Environ. Microbiol. 2011, 77, 7382–7393. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  107. Ray Mohapatra, A.; Jeevaratnam, K. Inhibiting bacterial colonization on catheters: Antibacterial and antibiofilm activities of bacteriocins from Lactobacillus plantarum SJ33. J. Glob. Antimicrob. Resist. 2019, 19, 85–92. [Google Scholar] [CrossRef]
  108. Khouiti, Z.; Simon, J.-P. Carnocin KZ213 produced by Carnobacterium piscicola 213 is adsorbed onto cells during growth. Its biosynthesis is regulated by temperature, pH and medium composition. J. Ind. Microbiol. Biotechnol. 2004, 31, 5–10. [Google Scholar] [CrossRef]
  109. Koné, A.P.; Zea, J.M.V.; Gagné, D.; Cinq-Mars, D.; Guay, F.; Saucier, L. Application of Carnobacterium maltaromaticum as a feed additive for weaned rabbits to improve meat microbial quality and safety. Meat Sci. 2018, 135, 174–188. [Google Scholar] [CrossRef]
  110. Moreno, M.F.; Sarantinopoulos, P.; Tsakalidou, E.; De Vuyst, L. The role and application of enterococci in food and health. Int. J. Food Microbiol. 2006, 106, 1–24. [Google Scholar] [CrossRef]
  111. Javed, A.; Masud, T.; ul Ain, Q.; Imran, M.; Maqsood, S. Enterocins of Enterococcus faecium, emerging natural food preservatives. Ann. Microbiol. 2011, 61, 699–708. [Google Scholar] [CrossRef]
  112. Sun, Z.; Harris, H.M.; McCann, A.; Guo, C.; Argimon, S.; Zhang, W.; Yang, X.; Jeffery, I.B.; Cooney, J.C.; Kagawa, T.F.; et al. Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera. Nat. Commun. 2015, 6, 8322. [Google Scholar] [CrossRef]
  113. Hill, D.; Sugrue, I.; Tobin, C.; Hill, C.; Stanton, C.; Ross, R.P. The Lactobacillus casei Group: History and Health Related Applications. Front. Microbiol. 2018, 9, 2107. [Google Scholar] [CrossRef] [Green Version]
  114. Yerlikaya, O. Probiotic potential and biochemical and technological properties of Lactococcus lactis ssp. lactis strains isolated from raw milk and kefir grains. J. Dairy Sci. 2019, 102, 124–134. [Google Scholar]
  115. Frantzen, C.A.; Kot, W.; Pedersen, T.B.; Ardö, Y.M.; Broadbent, J.R.; Neve, H.; Hansen, L.H.; Dal Bello, F.; Østlie, H.M.; Kleppen, H.P.; et al. Genomic Characterization of Dairy Associated Leuconostoc Species and Diversity of Leuconostocs in Undefined Mixed Mesophilic Starter Cultures. Front. Microbiol. 2017, 8, 132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  116. Björkroth, K.J.; Vandamme, P.; Korkeala, H.J. Identification and characterization of Leuconostoc carnosum, associated with production and spoilage of vacuum-packaged, sliced, cooked ham. Appl. Environ. Microbiol. 1998, 64, 3313–3319. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  117. Cho, Y.; Kim, E.; Lee, Y.; Han, S.K.; Kim, C.G.; Choo, D.W.; Kim, Y.R.; Kim, H.Y. Rapid and accurate identification of species of the genus Pediococcus isolated from Korean fermented foods by matrix-assisted laser desorption/ionization time-of-flight MS with local database extension. Int. J. Syst. Evol. Microbiol. 2017, 67, 744–752. [Google Scholar] [CrossRef] [PubMed]
  118. Papagianni, M.; Anastasiadou, S. Pediocins: The bacteriocins of Pediococci. Sources, production, properties and applications. Microb. Cell Factories 2009, 8, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  119. Eugster, E.; Fuchsmann, P.; Schlichtherle-Cerny, H.; Bütikofer, U.; Irmler, S. Formation of alanine, α-aminobutyrate, acetate, and 2-butanol during cheese ripening by Pediococcus acidilactici FAM18098. Int. Dairy J. 2019, 96, 21–28. [Google Scholar] [CrossRef]
  120. Cui, Y.; Xu, T.; Qu, X.; Hu, T.; Jiang, X.; Zhao, C. New Insights into Various Production Characteristics of Streptococcus thermophilus Strains. Int. J. Mol. Sci. 2016, 17, 1701. [Google Scholar] [CrossRef] [PubMed]
  121. Nes, I.F.; Diep, D.B.; Holo, H. Bacteriocin diversity in Streptococcus and Enterococcus. J. Bacteriol. 2007, 189, 1189–1198. [Google Scholar] [CrossRef] [Green Version]
  122. Kot, W.; Neve, H.; Heller, K.J.; Vogensen, F.K. Bacteriophages of Leuconostoc, Oenococcus, and Weissella. Front. Microbiol. 2014, 5, 186. [Google Scholar] [CrossRef] [Green Version]
  123. Oppegaård, C.; Fimland, G.; Anonsen, J.H.; Nissen-Meyer, J. The pediocin PA-1 accessory protein ensures correct disulfide bond formation in the antimicrobial peptide pediocin PA-1. Biochemistry 2015, 54, 2967–2974. [Google Scholar] [CrossRef]
  124. Cui, Y.; Zhang, C.; Wang, Y.; Shi, J.; Zhang, L.; Ding, Z.; Qu, X.; Cui, H. Class IIa bacteriocins: Diversity and new developments. Int. J. Mol. Sci. 2012, 13, 16668–16707. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  125. Nilsson, L.; Nielsen, M.K.; Ng, Y.; Gram, L. Role of acetate in production of an autoinducible class IIa bacteriocin in Carnobacterium piscicola A9b. Appl. Environ. Microbiol. 2002, 68, 2251–2260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  126. Fimland, G.; Eijsink, V.G.H.; Nissen-Meyer, J. Comparative studies of immunity proteins of pediocin-like bacteriocins. Microbiology 2002, 148, 3661–3670. [Google Scholar] [CrossRef] [Green Version]
  127. Martin-Visscher, L.A.; Sprules, T.; Gursky, L.J.; Vederas, J.C. Nuclear Magnetic Resonance Solution Structure of PisI, a Group B Immunity Protein that Provides Protection Against the Type IIa Bacteriocin Piscicolin 126, PisA. Biochemistry 2008, 47, 6427–6436. [Google Scholar] [CrossRef]
  128. Zhou, W.; Wang, G.; Wang, C.; Ren, F.; Hao, Y. Both IIC and IID Components of Mannose Phosphotransferase System Are Involved in the Specific Recognition between Immunity Protein PedB and Bacteriocin-Receptor Complex. PLoS ONE 2016, 11, e0164973. [Google Scholar] [CrossRef] [Green Version]
  129. Vaughan, A.; Eijsink, V.G.; Van Sinderen, D. Functional characterization of a composite bacteriocin locus from malt isolate Lactobacillus sakei 5. Appl. Environ. Microbiol. 2003, 69, 7194–7203. [Google Scholar] [CrossRef] [Green Version]
  130. Diep, D.B.; Havarstein, L.S.; Nes, I.F. Characterization of the locus responsible for the bacteriocin production in Lactobacillus plantarum C11. J. Bacteriol. 1996, 178, 4472–4483. [Google Scholar] [CrossRef] [Green Version]
  131. Diep, D.B.; Johnsborg, O.; Risøen, P.A.; Nes, I.F. Evidence for dual functionality of the operon plnABCD in the regulation of bacteriocin production in Lactobacillus plantarum. Mol. Microbiol. 2001, 41, 633–644. [Google Scholar] [CrossRef]
  132. Straume, D.; Kjos, M.; Nes, I.F.; Diep, D.B. Quorum-sensing based bacteriocin production is down-regulated by N-terminally truncated species of gene activators. Mol. Genet. Genom. 2007, 278, 283–293. [Google Scholar] [CrossRef]
  133. Maldonado, A.; Jiménez-Díaz, R.; Ruiz-Barba, J.L. Induction of plantaricin production in Lactobacillus plantarum NC8 after coculture with specific gram-positive bacteria is mediated by an autoinduction mechanism. J. Bacteriol. 2004, 186, 1556–1564. [Google Scholar] [CrossRef] [Green Version]
  134. Kjos, M.; Borrero, J.; Opsata, M.; Birri, D.J.; Holo, H.; Cintas, L.M.; Snipen, L.; Hernandez, P.E.; Nes, I.F.; Diep, D.B. Target recognition, resistance, immunity and genome mining of class II bacteriocins from Gram-positive bacteria. Microbiology 2011, 157, 3256–3267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  135. Oppegård, C.; Emanuelsen, L.; Thorbek, L.; Fimland, G.; Nissen-Meyer, J. The lactococcin G immunity protein recognizes specific regions in both peptides constituting the two-peptide bacteriocin lactococcin G. Appl. Environ. Microbiol. 2010, 76, 1267–1273. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  136. Britton, A.P.; van der Ende, S.R.; van Belkum, M.J.; Martin-Visscher, L.A. The membrane topology of immunity proteins for the two-peptide bacteriocins carnobacteriocin XY, lactococcin G, and lactococcin MN shows structural diversity. MicrobiologyOpen 2020, 9, e00957. [Google Scholar] [CrossRef] [PubMed]
  137. Cebrián, R.; Martínez-Bueno, M.; Valdivia, E.; Albert, A.; Maqueda, M.; Sánchez-Barrena, M.J. The bacteriocin AS-48 requires dimer dissociation followed by hydrophobic interactions with the membrane for antibacterial activity. J. Struct. Biol. 2015, 190, 162–172. [Google Scholar] [CrossRef]
  138. Sanchez-Barrena, M.J.; Martinez-Ripoll, M.; Galvez, A.; Valdivia, E.; Maqueda, M.; Cruz, V.; Albert, A. Structure of bacteriocin AS-48: From soluble state to membrane bound state. J. Mol. Biol. 2003, 334, 541–549. [Google Scholar] [CrossRef]
  139. González, C.; Langdon, G.M.; Bruix, M.; Gálvez, A.; Valdivia, E.; Maqueda, M.; Rico, M. Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally related to mammalian NK-lysin. Proc. Natl. Acad. Sci. USA 2000, 97, 11221–11226. [Google Scholar] [CrossRef] [Green Version]
  140. Cebrián, R.; Maqueda, M.; Neira, J.L.; Valdivia, E.; Martínez-Bueno, M.; Montalbán-López, M. Insights into the Functionality of the Putative Residues Involved in Enterocin AS-48 Maturation. Appl. Environ. Microbiol. 2010, 76, 7268–7276. [Google Scholar] [CrossRef] [Green Version]
  141. Perez, R.H.; Sugino, H.; Ishibashi, N.; Zendo, T.; Wilaipun, P.; Leelawatcharamas, V.; Nakayama, J.; Sonomoto, K. Mutations near the cleavage site of enterocin NKR-5-3B prepeptide reveal new insights into its biosynthesis. Microbiology 2017, 163, 431–441. [Google Scholar] [CrossRef]
  142. van Belkum, M.J.; Martin-Visscher, L.A.; Vederas, J.C. Structure and genetics of circular bacteriocins. Trends Microbiol. 2011, 19, 411–418. [Google Scholar] [CrossRef]
  143. Kawai, Y.; Kusnadi, J.; Kemperman, R.; Kok, J.; Ito, Y.; Endo, M.; Arakawa, K.; Uchida, H.; Nishimura, J.; Kitazawa, H.; et al. DNA sequencing and homologous expression of a small peptide conferring immunity to gassericin A, a circular bacteriocin produced by Lactobacillus gasseri LA39. Appl. Environ. Microbiol. 2009, 75, 1324–1330. [Google Scholar] [CrossRef] [Green Version]
  144. Martínez-Bueno, M.; Valdivia, E.; Gálvez, A.; Coyette, J.; Maqueda, M. Analysis of the gene cluster involved in production and immunity of the peptide antibiotic AS-48 in Enterococcus faecalis. Mol. Microbiol. 1998, 27, 347–358. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  145. van Belkum, M.J.; Martin-Visscher, L.A.; Vederas, J.C. Cloning and Characterization of the Gene Cluster Involved in the Production of the Circular Bacteriocin Carnocyclin A. Probiotics Antimicrob. Proteins 2010, 2, 218–225. [Google Scholar] [CrossRef] [PubMed]
  146. Gabrielsen, C.; Brede, D.A.; Nes, I.F.; Diep, D.B. Circular bacteriocins: Biosynthesis and mode of action. Appl. Environ. Microbiol. 2014, 80, 6854–6862. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  147. Acedo, J.Z.; van Belkum, M.J.; Lohans, C.T.; Towle, K.M.; Miskolzie, M.; Vederas, J.C. Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity. Biochemistry 2016, 55, 733–742. [Google Scholar] [CrossRef] [PubMed]
  148. Gajic, O.; Buist, G.; Kojic, M.; Topisirovic, L.; Kuipers, O.P.; Kok, J. Novel Mechanism of Bacteriocin Secretion and Immunity Carried Out by Lactococcal Multidrug Resistance Proteins. J. Biol. Chem. 2003, 278, 34291–34298. [Google Scholar] [CrossRef] [Green Version]
  149. Iwatani, S.; Horikiri, Y.; Zendo, T.; Nakayama, J.; Sonomoto, K. Bifunctional gene cluster lnqBCDEF mediates bacteriocin production and immunity with differential genetic requirements. Appl. Environ. Microbiol. 2013, 79, 2446–2449. [Google Scholar] [CrossRef] [Green Version]
  150. Ladjouzi, R.; Lucau-Danila, A.; Benachour, A.; Drider, D. A Leaderless Two-Peptide Bacteriocin, Enterocin DD14, Is Involved in Its Own Self-Immunity: Evidence and Insights. Front. Bioeng. Biotechnol. 2020, 8, 644. [Google Scholar] [CrossRef]
  151. Kristiansen, P.E.; Persson, C.; Fuochi, V.; Pedersen, A.; Karlsson, G.B.; Nissen-Meyer, J.; Oppegård, C. Nuclear Magnetic Resonance Structure and Mutational Analysis of the Lactococcin a Immunity Protein. Biochemistry 2016, 55, 6250–6257. [Google Scholar] [CrossRef]
  152. Wang, J.; Xu, H.; Liu, S.; Song, B.; Liu, H.; Li, F.; Deng, S.; Wang, G.; Zeng, H.; Zeng, X.; et al. Toyoncin, a novel leaderless bacteriocin that is produced by Bacillus toyonensis XIN-YC13 and specifically targets B. Cereus and Listeria monocytogenes. Appl. Environ. Microbiol. 2021, 87, e00185-21. [Google Scholar] [CrossRef]
  153. Iwatani, S.; Ishibashi, N.; Flores, F.P.; Zendo, T.; Nakayama, J.; Sonomoto, K. LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5. FEMS Microbiol. Lett. 2016, 363, fnw200. [Google Scholar] [CrossRef] [Green Version]
  154. Criado, R.; Gutiérrez, J.; Martín, M.; Herranz, C.; Hernández, P.E.; Cintas, L.M. Immunochemical characterization of temperature-regulated production of enterocin L50 (EntL50A and EntL50B), enterocin P, and enterocin Q by Enterococcus faecium L50. Appl. Environ. Microbiol. 2006, 72, 7634–7643. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  155. Masuda, Y.; Perez, R.H.; Zendo, T.; Sonomoto, K. Nutrition-adaptive control of multiple-bacteriocin production by Weissella hellenica QU 13. J. Appl. Microbiol. 2016, 120, 70–79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  156. Telke, A.A.; Ovchinnikov, K.V.; Vuoristo, K.S.; Mathiesen, G.; Thorstensen, T.; Diep, D.B. Over 2000-Fold Increased Production of the Leaderless Bacteriocin Garvicin KS by Increasing Gene Dose and Optimization of Culture Conditions. Front. Microbiol. 2019, 10, 389. [Google Scholar] [CrossRef]
  157. Sidooski, T.; Brandelli, A.; Bertoli, S.L.; Souza, C.K.d.; Carvalho, L.F.d. Physical and nutritional conditions for optimized production of bacteriocins by lactic acid bacteria—A review. Crit. Rev. Food Sci. Nutr. 2019, 59, 2839–2849. [Google Scholar] [CrossRef]
  158. Abbasiliasi, S.; Tan, J.S.; Ibrahim, T.A.T.; Bashokouh, F.; Ramakrishnan, N.R.; Mustafa, S.; Ariff, A.B. Fermentation factors influencing the production of bacteriocins by lactic acid bacteria: A review. RSC Adv. 2017, 7, 29395–29420. [Google Scholar] [CrossRef]
  159. Fahim, H.A.; Rouby, W.M.A.E.; El-Gendy, A.O.; Khairalla, A.S.; Naguib, I.A.; Farghali, A.A. Enhancement of the productivity of the potent bacteriocin avicin A and improvement of its stability using nanotechnology approaches. Sci. Rep. 2017, 7, 10604. [Google Scholar] [CrossRef] [Green Version]
  160. Li, C.; Bai, J.; Cai, Z.; Ouyang, F. Optimization of a cultural medium for bacteriocin production by Lactococcus lactis using response surface methodology. J. Biotechnol. 2002, 93, 27–34. [Google Scholar] [CrossRef]
  161. Avonts, L.; Van Uytven, E.; De Vuyst, L. Cell growth and bacteriocin production of probiotic Lactobacillus strains in different media. Int. Dairy J. 2004, 14, 947–955. [Google Scholar] [CrossRef]
  162. Maldonado-Barragán, A.; West, S.A. The cost and benefit of quorum sensing-controlled bacteriocin production in Lactobacillus plantarum. J. Evol. Biol. 2020, 33, 101–111. [Google Scholar] [CrossRef]
  163. Man, L.-L.; Xiang, D.-J. LuxS-mediated quorum sensing system in Lactobacillus plantarum NMD-17 from koumiss: Induction of plantaricin MX in co-cultivation with certain lactic acid bacteria. Folia Microbiol. 2021, 66, 855–871. [Google Scholar] [CrossRef]
  164. Piazentin, A.C.M.; Mendonça, C.M.N.; Vallejo, M.; Mussatto, S.I.; de Souza Oliveira, R.P. Bacteriocin-like inhibitory substances production by Enterococcus faecium 135 in co-culture with Ligilactobacillus salivarius and Limosilactobacillus reuteri. Braz. J. Microbiol. 2022, 53, 131–141. [Google Scholar] [CrossRef] [PubMed]
  165. Gutiérrez-Cortés, C.; Suarez, H.; Buitrago, G.; Nero, L.A.; Todorov, S.D. Enhanced Bacteriocin Production by Pediococcus pentosaceus 147 in Co-culture with Lactobacillus plantarum LE27 on Cheese Whey Broth. Front. Microbiol. 2018, 9, 2952. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  166. Jawan, R.; Abbasiliasi, S.; Tan, J.S.; Mustafa, S.; Halim, M.; Ariff, A.B. Influence of culture conditions and medium compositions on the production of bacteriocin-like inhibitory substances by Lactococcus lactis Gh1. Microorganisms 2020, 8, 1454. [Google Scholar] [CrossRef] [PubMed]
  167. Lajis, A.F.B. Biomanufacturing process for the production of bacteriocins from Bacillaceae family. Bioresour. Bioprocess. 2020, 7, 8. [Google Scholar] [CrossRef]
  168. Delgado, A.; Arroyo López, F.N.; Brito, D.; Peres, C.; Fevereiro, P.; Garrido-Fernández, A. Optimum bacteriocin production by Lactobacillus plantarum 17.2b requires absence of NaCl and apparently follows a mixed metabolite kinetics. J. Biotechnol. 2007, 130, 193–201. [Google Scholar]
  169. Parlindungan, E.; May, B.K.; Jones, O.A.H. Metabolic Insights into the Effects of Nutrient Stress on Lactobacillus plantarum B21. Front. Mol. Biosci. 2019, 6, 75. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  170. Neysens, P.; Messens, W.; De Vuyst, L. Effect of sodium chloride on growth and bacteriocin production by Lactobacillus amylovorus DCE 471. Int. J. Food Microbiol. 2003, 88, 29–39. [Google Scholar] [CrossRef]
  171. Abo-Amer, A.E. Optimization of bacteriocin production by Lactobacillus acidophilus AA11, a strain isolated from Egyptian cheese. Ann. Microbiol. 2011, 61, 445–452. [Google Scholar] [CrossRef]
  172. Radha, K.; Padmavathi, T. Statistical optimization of bacteriocin produced from Lactobacillus delbrueckii subsp bulgaricus isolated from yoghurt. Int. Food Res. J. 2017, 24, 803–809. [Google Scholar]
  173. Suganthi, V.; Mohanasrinivasan, V. Optimization studies for enhanced bacteriocin production by Pediococcus pentosaceus KC692718 using response surface methodology. J. Food Sci. Technol. 2015, 52, 3773–3783. [Google Scholar] [CrossRef]
  174. Wang, P.; Wang, T.; Ismael, M.; Wang, X.; Yi, Y.; Lü, X. Development of an electroporation method and expression patterns of bacteriocin-encoding genes in Companilactobacillus crustorum MN047. Food Biosci. 2021, 44, 101420. [Google Scholar] [CrossRef]
  175. Borrero, J.; Jiménez, J.J.; Gútiez, L.; Herranz, C.; Cintas, L.M.; Hernández, P.E. Use of the usp45 lactococcal secretion signal sequence to drive the secretion and functional expression of enterococcal bacteriocins in Lactococcus lactis. Appl. Microbiol. Biotechnol. 2011, 89, 131–143. [Google Scholar] [CrossRef] [PubMed]
  176. Arbulu, S.; Jiménez, J.J.; Gútiez, L.; Cintas, L.M.; Herranz, C.; Hernández, P.E. Cloning and Expression of Synthetic Genes Encoding the Broad Antimicrobial Spectrum Bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by Recombinant Pichia pastoris. BioMed Res. Int. 2015, 2015, 767183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  177. Tang, X.; Wu, S.; Wang, X.; Gu, Q.; Li, P. Antimicrobial activity and preliminary mode of action of PlnEF expressed in Escherichia coli against Staphylococci. Protein Expr. Purif. 2018, 143, 28–33. [Google Scholar] [CrossRef] [PubMed]
  178. Yu, W.; Ma, J.; Chen, X.; Tan, Y.; Chen, P.; Zhu, X.; Liu, L. Expression and purification of recombinant Lactobacillus casei bacteriocin and analysis of its antibacterial activity. Cyta-J. Food 2020, 18, 301–308. [Google Scholar] [CrossRef]
  179. Acuña, L.; Corbalán, N.; Quintela-Baluja, M.; Barros-Velázquez, J.; Bellomio, A. Expression of the hybrid bacteriocin Ent35-MccV in Lactococcus lactis and its use for controlling Listeria monocytogenes and Escherichia coli in milk. Int. Dairy J. 2020, 104, 104650. [Google Scholar] [CrossRef]
  180. O’Connor, P.M.; Kuniyoshi, T.M.; Oliveira, R.P.; Hill, C.; Ross, R.P.; Cotter, P.D. Antimicrobials for food and feed; a bacteriocin perspective. Curr. Opin. Biotechnol. 2020, 61, 160–167. [Google Scholar] [CrossRef]
Figure 1. A schematic diagram of the biosynthesis of class IIa bacteriocins.
Figure 1. A schematic diagram of the biosynthesis of class IIa bacteriocins.
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Figure 2. Organization of biosynthetic gene clusters of class IIa bacteriocins of LAB.
Figure 2. Organization of biosynthetic gene clusters of class IIa bacteriocins of LAB.
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Figure 3. A schematic diagram of the biosynthesis of plantaricinE/F and plantaricinJ/K.
Figure 3. A schematic diagram of the biosynthesis of plantaricinE/F and plantaricinJ/K.
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Figure 4. Organization of biosynthetic gene clusters of class IIb bacteriocins of LAB.
Figure 4. Organization of biosynthetic gene clusters of class IIb bacteriocins of LAB.
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Figure 5. Organization of biosynthetic gene clusters of class IIc bacteriocins of LAB.
Figure 5. Organization of biosynthetic gene clusters of class IIc bacteriocins of LAB.
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Figure 6. Organization of biosynthetic gene clusters of class IId bacteriocins of LAB.
Figure 6. Organization of biosynthetic gene clusters of class IId bacteriocins of LAB.
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Table 1. Amino acids sequences of class II bacteriocins.
Table 1. Amino acids sequences of class II bacteriocins.
Name of BacteriocinsSequenceProducer SpeciesStrainReference
ClassIIa
Acidocin AMISMISSHQKTLTDKELALISGGKTYYGTNGVHCTKRSLWGKVRLKNVIPGTLCRKQSLPIKQDLKILLGWATGAFGKTFHLactobacillus acidophilusTK9201[19]
Bacteriocin 31MKKKLVICGIIGIGFTALGTNVEAATATYYGNGLYCNKQKCWVDWNKASREIGKIIVNGWVQHGPWAPREnterococcus faecalisYI717[20]
Bacteriocin BM1MKSVKELNKKEMQQINGGAISYGNGVYCNKEKCWVNKAENKQAITGIVIGGWASSLAGMGHCarnobacterium piscicolaLV17B[21]
Bacteriocin B2MNSVKELNVKEMKQLHGGVNYGNGVSCSKTKCSVNNGQAFQERYTAGINSFVSGVASGAGSIGRRPCarnobacterium piscicolaLV17B[21]
Bacteriocin T8MKKKVLKHCVILGILGTCLAGIGTGIKVDAATYYGNGLYCNKEKCWVDWNQAKGEIGKIIVNGWVNHGPWAPRREnterococcus faeciumT8[22]
Carnobacteriocin B2MNSVKELNVKEMKQLHGGVNYGNGVSCSKTKCSVNWGQAFQERYTAGINSFVSGVASGAGSIGRRPCarnobacterium piscicolaLV17[23]
Carnobacteriocin BM1MKSVKELNKKEMQQIIGGAISYGNGVYCNKEKCWVNKAENKQAITGIVIGGWASSLAGMGHCarnobacterium piscicolaLV17B[21]
Curvacin AMNNVKELSMTELQTITGGARSYGNGVYCNNKKCWVNRGEATQSIIGGMISGWASGLAGMLatilactobacillus curvatusLTH1174[24]
Divercin V41MKNLKEGSYTAVNTDELKSINGGTKYYGNGVYCNSKKCWVDWGQASGCIGQTVVGGWLGGAIPGKCCarnobacterium divergensV41[25]
Enterocin AMKHLKILSIKETQLIYGGTTHSGKYYGNGVYCTKNKCTVDWAKATTCIAGMSIGGFLGGAIPGKCEnterococcus faeciumCTCA92/T136[26]
Enterocin CRL35MKKLTSKEMAQVVGGKYYGNGVSCNKKGCSVDWGKAIGIIGNNSAANLATGGAAGWKSEnterococcus faeciumCRL 35[27]
Enterocin HFMEKLTVKEMSQVVGGKYYGNGVSCNKKGCSVDWGKAIGIIGNNAAANLTTGGKAGWKGEnterococcus faeciumM3K31[28]
Enterocin PMRKKLFSLALIGIFGLVVTNFGTKVDAATRSYGNGVYCNNSKCWVNWGEAKENIAGIVISGWASGLAGMGHEnterococcus faeciumP13[29]
Enterocin SE-K4MKKKLVKGLVICGMIGIGFTALGTNVEAATYYGNGVYCNKQKCWVDWSRARSEIIDRGVKAYVNGFTKVLGEnterococcus faecalisK-4[30]
Leucocin AMMNMKPTESYEQLDNSALEQVVGGKYYGNGVHCTKSGCSVNWGEAFSAGVHRLANGGNGFWLeuconostoc gelidumUAL 187[31]
Mesentericin Y105MTNMKSVEAYQQLDNQNLKKVVGGKYYGNGVHCTKSGCSVNWGEAASAGIHRLANGGNGFWLeuconostoc mesenteroidesY105[32]
Mundticin KSMKKLTAKEMSQVVGGKYYGNGVSCNKKGCSVDWGKAIGIIGNNSAANLATGGAAGWKSEnterococcus mundtiiNFRI 7393[33]
Pediocin PA-1MKKIEKLTEKEMANIIGGKYYGNGVTCGKHSCSVDWGKATTCIINNGAMAWATGGHQGNHKCPediococcus acidilacticiPAC 1.0[34]
Piscicolin 126MKTVKELSVKEMQLTTGGKYYGNGVSCNKNGCTVDWSKAIGIIGNNAAANLTTGGAAGWNKGCarnobacterium piscicolaJG126[35]
Plantaricin 423MMKKIEKLTEKEMANIIGGKYYGNGVTCGKHSCSVNWGQAFSCSVSHLANFGHGKCLactiplantibacillus plantarum423[36]
Sakacin AMNNVKELSMTELQTITGGARSYGNGVYCNNKKCWVNRGEATQSIIGGMISGWASGLAGMLatilactobacillus sakei706[37]
Sakacin PMEKFIELSLKEVTAITGGKYYGNGVHCGKHSCTVDWGTAIGNIGNNAAANWATGGNAGWNKLatilactobacillus sakeiMI401[38]
Sakacin GMKNTRSLTIQEIKSITGGKYYGNGVSCNSHGCSVNWGQAWTCGVNHLANGGHGGVCLatilactobacillus sakei2512[39]
Bacteriocin L-1077TNYGNGVGVPDAIMAGIIKLIFIFNIRQGYNFGKKATLigilactobacillus salivarius1077[40]
Bavaricin MNTKYYGNGVYCNSKKCWVDWGQAAGGIGQTVVXGWLGGAIPGKLactobacillus bavaricusMN[41]
Bavaricin AKYYGNGVHCGKHSCTVDWGTAIGNIGNNAAANXATGXNAGGLatilactobacillus sakeiMI401[42]
Bifidocin BKYYGNGVTCGLHDCRVDRGKATCGIINNGGMWGDIGBifidobacterium bifidumNCFB 1454[43]
Lactococcin MMFIITSYGNGVHCNKSKCWIDVSELETYKAGTVSNPKDILWLactococcus lactisMMFII[44]
Leucocin CKNYGNGVHCTKKGCSVDWGYAWTNIANNSVMNGLTGGNAGWHNLeuconostoc mesenteroidesTA33a[45]
MundticinKYYGNGVSCNKKGCSVDWGKAIGIIGNNSAANLATGGAAGWSKEnterococcus mundtiiATO6[33]
Piscicocin VIaKYYGNGVSCNKNGCTVDWSKAIGIIGNNAAANLTTGGAAGWNKGCarnobacterium piscicolaV1[46]
Plantaricin C19KYYGNGLSCSKKGCTVNWGQAFSCGVNRVATAGHGKLactiplantibacillus plantarumC19[47]
plantaricin LPL-1VIADKYYGNGVSCGKHTCTVDWGEAFSCSVSHLANFGHGKCLactiplantibacillus plantarumLPL-1[48]
Class IIb
ABP-118118αMMKEFTVLTECELAKVDGGKRGPNCVGNFLGGLFAGAAAGVPLGPAGIVGGANLGMVGGALTCLLigilactobacillus salivariusUCC118[49]
118βMKNLDKRFTIMTEDNLASVNGGKNGYGGSGNRWVHCGAGIVGGALIGAIGGPWSAVAGGISGGFTSCR
Amylovorin LamyLaMSKGEVLNEDELTAVVGGSKGKGRNNWAGNTIGIVSSAATGAALGSAICGPGCGFVGAHWGAVGWTAVASFSGAFGKIRKLactobacillus amylovorusDCE 471[50]
amyLbMKQLNSEQLQNIIGGNRWTNAYSAALGCAVPGVKYGKKLGGVWGAVIGGVGGAAVCGLAGYVRKG
Acidocin LF221BLF221BMIEKVSKNELSRIYGGNNVNWGSVAGSCGKGAVMEIYFGNPILGCANGAATSLVLQTASGIYKNYQKKRLactobacillus gasseriLF221[51]
LF221βMALKTLEKHELRNVMGGNKWGNAVIGAATGATRGVSWCRGFGPWGMTACALGGAAIGGYLGYKSN
Brevicin 174A174A-βMEKFAVLSLSDLVDIQGGKKKKKYTGPNYRCMVKSGGGLVSGAIGGSPFGVGGIVGGGMAGLVGGAISCLNNKLevilactobacillus brevis174A[52]
174A-γMYKELTVDELALIDGGKKKKKKVACTWGNAATAAASGAVKGILGGPTGALAGAIWGVSQCASNNLHGMH
Carnobacteriocin XYCbnXMKSVKELNVKEMQQTIGGWGWKEVVQNGQTIFSAGQKLGNMVGKIVPLPFGCarnobacteria [53]
CbnYMNKEFKSLNEVEMKKINGGSAILAITLGIFATGYGMGVQKAINDRRKK
Enterocin XEntXαMQNVKEVSVKEMKQIIGGSNDSLWYGVGQFMGKQANCITNHPVKHMIIPGYCLSKILGEnterococcus faeciumKU-B5[54]
EntXβMKKYNELSKKELLQIQGGIAPIIVAGLGYLVKDAWDHSDQIISGFKKGWNGGRRK
Enterocin 1071EntαMKQYKVLNEKEMKKPIGGESVFSKIGNAVGPAAYWILKGLGNMSDVNQADRINRKKHEnterococcus faecalisFAIR-E 309[55]
EntβMKNIKNASNIKVIEDNELKAITGGGPGKWLPWLQPAYDFVTGLAKGIGKEGNKNKWKNV
Gassericin SGasAMKVLNECQLQTVVGGKNWSVAKCGGTIGTNIAIGAWRGARAGSFFGQPVSVGAGALIGASAGAIGGSVQCVGWLAGGGRLactobacillus gasseriLA327[56]
GasXMIEKVSKNELSRIYGGNNVNWGSVAGSCGKGAVMGIYFGNPILGCANGAATSLVLQTTSGIYKNYQKKR
Gassericin TGatAMKNFNTLSFETLANIVGGRNNWAANIGGVGGATVAGWALGNAVCGPACGFVGAHYVPIAWAGVTAATGGFGKIRKLactobacillus gasseriLA327[56]
GatXMALKTLEKHELRNVMGGNKWGNAVIGAATGATRGVSWCRGFGPWGMTACGLGGAAIGGYLGYKSN
Mutacin IVnlm AMDTQAFEQFDVMDSQTLSTVEGGKVSGGEAVAAIGICATASAAIGGLAGATLVTPYCVGTWGLIRSHStreptococcus mutansUA159[57]
nlm BMELNVNNYKSLTNDELSEVFGGDKQAADTFLSAVGGAASGFTYCASNGVWHPYILAGCAGVGAVGSVVFPH
Lactococcin GLcnGαMKELSEKELRECVGGGTWDDIGQGIGRVAYWVGKAMGNMSDVNQASRINRKKKHLactococcus lactis [58]
LcnGβMKNNNNFFKGMEIIEDQELVSITGGKKWGWLAWVDPAYEFIKGFGKGAIKEGNKDKWKNI
Lactococcin QLcnQαMKELSEKELRECVGGSIWGDIGQGVGKAAYWVGKAMGNMSDVNQASRINRKKKHLactococcus lactisQU4[59]
LcnQβMKNNNNNFFKDMEIIEDQELVSITGGKKWGWLAWVEPAGEFLKGFGKGAIKEGNKDKWKNI
Lactocin 705705αMESNKLEKFANISNKDLNKITGGGFWGGLGYIAGRVGAAYGHAQASANNHHSPINGLacticaseibacillus caseiCRL 705[60]
705βMDNLNKFKKLSDNKLQATIGGGMSGYIQGIPDFLKGYLHGISAANKHKKGRLGY
Plantaricin NC8PlnC8αMDKFEKISTSNLEKISGGDLTTKLWSSWGYYLGKKARWNLKHPYVQFLactiplantibacillus plantarumNC8[61]
PlnC8βMNNLNKFSTLGKSSLSQIEGGSVPTSVYTLGIKILWSAYKHRKTIEKSFNKGFYH
Plantaricin SPlsαMNNALSFEQQFTDFSTLSDSELESVEGGRNKLAYNMGHYAGKATIFGLAAWALLALactiplantibacillus plantarumLPCO10[62]
PlsβMDKIIKFQGISDDQLNAVIGGKKKKQSWYAAAGDAIVSFGEGFLNAW
Plantaricin EFPlnEMLQFEKLQYSRLPQKKLAKISGGFNRGGFNRGGYNFGKSVRHVVDAIGSVAGIRGILKSIRLactiplantibacillus plantarumC11[63]
PlnFMKKFLVLRDRELNAISGGVFHAYSARGVRNNYKSAVGPADWVISAVRGFIHG
Plantaricin JKPlnJMTVNKMIKDLDVVDAFAPISNNKLNGVVGGGAWKNFWSSLRKGFYDGEAGRAIRRLactiplantibacillus plantarumC11[64]
PlnKMKIKLTVLNEFEELTADAEKNISGGRRSRKNGIGYAIGYAFGAVERAVLGGSRDYNK
Salivaricin PSalPαMMKEFTVLTECELAKVDGGKRGPNCVGNFLGGLFAGAAAGVPLGPAGIVGGANLGMVGGALTCLLigilactobacillus salivariusDPC6005[65]
SalPβMKNLDKRFTIMTEDNLASVNGGKNGYGGSGNRWVHCGAGIVGGALIGAIGGPWSAVAGGISGGFASCH
Thermophilin 13ThmAMNTITICKFDVLDAELLSTVEGGYSGKDCLKDMGGYALAGAGSGALWGAPAGGVGALPGAFVGAHVGAIAGGFACMGGMIGNKFNStreptococcus thermophilesSPi13[66]
ThmBMKQYNGFEVLHELDLANVTGGQINWGSVVGHCIGGAIIGGAFSGGAAAGVGCLVGSGKAIINGL
UncharacterizedLSEI_2392MYTMTNLKDKELSQITGGFAFGIPVAAILGFLASDAWSHADEIAGGATSGWSLADKSHSLLacticaseibacillus caseiATCC 334[67]
LSEI_2393MQQFMTLDNSSLEKIAGGENGGLWSIIGFGLGFSARSVLTGSLFVPSRGPVIDLVKQLTPKN
UncharacterizedLSEI_2405MISKEVGITLKQHDLVLIQGGAKRRNKPSGCIVSTIGGAVAGAAGLNPFTTVAGAAIGLSLPRLQLacticaseibacillus caseiATCC 334[67]
LSEI_2406MSYNYRQIDDFQLSGVSGGKKKFDCAATFVTGITAGIGSGTITGLAGGPFGIIGGAVVGGNLGAVGSAIKCLGDGMQ
Class IIc
Carnocyclin-AMLYELVAYGIAQGTAEKVVSLINAGLTVGSIISILGGVTVGLSGVFTAVKAAIAKQGIKKAIQLCarnobacterium maltaromaticumUAL307[68]
Enterocin NKR-5-3BMKKNLLLVLPIVGIVGLFVGAPMLTANLGISSYAAKKVIDIINTGSAVATIIALVTAVVGGGLITAGIVATAKSLIKKYGAKYAAAWEnterococcus faeciumNKR-5-3[69]
Enterocin AS-48MVKENKFSKIFILMALSFLGLALFSASLQFLPIAHMAKEFGIPAAVAGTVLNVVEAGGWVTTIVSILTAVGSGGLSLLAAAGRESIKAYLKKEIKKKGKRAVIAWEnterococcus faecalisS-48[70]
Garvicin MLMFDLVATGMAAGVAKTIVNAVSAGMDIATALSLFSGAFTAAGGIMALIKKYAQKKLWKQLIAALactococcus garvieaeDCC43[71]
Leucocyclicin QMFLVNQLGISKSLANTILGAIAVGNLASWLLALVPGPGWATKAALATAETIVKHEGKAAAIAWLeuconostoc mesenteroidesTK41401[72]
Lactocyclicin QMFLIDHLGAPRWAVDTILGAIAVGNLASWVLALVPGPGWAVKAGLATAAAIVKHQGKAAAAAWLactococcus sp.QU 12[73]
Plantaricyclin AMLSAYRSKLGLNKFEVTVLMIISLFILLFATVNIVWIAKQFGVHLTTSLTQKALDLLSAGSSLGTVAAAVLGVTLPAWAVAAAGALGGTAALactiplantibacillus plantarumNI326[74]
Plantacyclin B21AGMLSAYRSRLGLNKFEVAILMIISLFILLFATVNIVWIARQFGVHLTTKLTQKALDLLSSGASLGTVAAVILGVTLPGWAVAAAGALGGTAALactiplantibacillus plantarumB21[75]
UberolysinMDILLELAGYTGIASGTAKKVVDAIDKGAAAFVIISIISTVISAGALGAVSASADFIILTVKNYISRNLKAQAVIWStreptococcus uberis42[76]
Acidocin BMVTKYGRNLGLSKVELFAIWAVLVVALLLATANIYWIADQFGIHLATGTARKLLDAVASGASLGTAFAAILGVTLPAWALAAAGALGATAALactobacillus acidophilusM46[77]
Gassericin AMVTKYGRNLGLNKVELFAIWAVLVVALLLTTANIYWIADQFGIHLATGTARKLLDAMASGASLGTAFAAILGVTLPAWALAAAGALGATAALactobacillus gasseriLA39[78]
Reutericin 6MVTKYGRNLGLNKVELFAIWAVLVVALLLTTANIYWIADQFGIHLATGTARKLLDAMASGASLGTAFAAILGVTLPAWALAAAGALGATAALimosilactobacillus reuteriLA 6[79]
Class IId (leaderless)
Bacteriocin LS2TNWKKIGKCYAGTLGSAVLGFGAMGPVGYWAGAGVGYASFCLigilactobacillus salivariusBGHO1[80]
Enterocin EJ97MLAKIKAMIKKFPNPYTLAAKLTTYEINWYKQQYGRYPWERPVAEnterococcus faecalisEJ97[81]
Enterocin QMNFLKNGIAKWMTGAELQAYKKKYGCLPWEKISCEnterococcus faeciumL50[82]
LsbBMKTILRFVAGYDIASHKKKTGGYPWERGKALactococcus lactisBGMN1-5[83]
Lacticin QMAGFLKVVQLLAKYGSKAVQWAWANKGKILDWLNAGQAIDWVVSKIKQILGIKLactococcus lactisQU 5[84]
Lacticin ZMAGFLKVVQILAKYGSKAVQWAWANKGKILDWINAGQAIDWVVEKIKQILGIKLactococcus lactisQU 14[85]
Lactolisterin BUMWGRILGTVAKYGPKAVSWAWQHKWELINMGDLAFRYIQRIWGLactococcus lactisBGBU1-4[86]
Weisselicin YMANIVLRVGSVAYNYAPKIFKWIGEGVSYNQIIKWGHNKGWWWeissella hellenicaQU 13[87]
Weisselicin MMVSAAKVALKVGWGLVKKYYTKVMQFIGEGWSVDQIADWLKRHWeissella hellenicaQU 13[87]
Enterocin L50L50AMGAIAKLVAKFGWPIVKKYYKQIMQFIGEGWAINKIIEWIKKHIEnterococcus faecalisL50[88]
L50BMGAIAKLVTKFGWPLIKKFYKQIMQFIGQGWTIDQIEKWLKRH
Enterocin MR10MR10AMGAIAKLVAKFGWPIVKKYYKQIMQFIGEGWAINKIIDWIKKHIEnterococcus faecalisMRR 10-3[89]
MR10BMGAIAKLVAKFGWPFIKKFYKQIMQFIGQGWTIDQIEKWLKRH
Garvicin KSKS-AMGAIIKAGAKIVGKGVLGGGASWLGWNVGEKIWKLactococcus garvieaeKS1546[90]
KS-BMGAIIKAGAKIIGKGLLGGAAGGATYGGLKKIFG
KS-CMGAIIKAGAKIVGKGALTGGGVWLAEKLFGGK
ClassIId (non-pediocin liner bacteriocins)
Bovicin 255MNTKTFEQFDVMTDEALSTVEGGGKGYCKPVYYAANGYSCRYSNGEWGYVVTKGAFQATTDVIANGWVSSLGGGYFGKPStreptococcus bovisLRC 0255[91]
Enterocin 96MLNKKLLENGVVNAVTIDELDAQFGGMSKRDCNLMKACCAGQAVTYAIHSLLNRLGGDSSDPAGCNDIVRKYCKEnterococcus faecalisWHE 96[92]
Garvieacin QMENKNYTVLSDEELQKIDGGEYHLMNGANGYLTRVNGKYVYRVTKDPVSAVFGVISNGWGSAGAGFGPQHLactococcus garvieaeBCC 43578[93]
Garvicins AMENNNYTVLSDEELQKIDGGIGGALGNALNGLGTWANMMNGGGFVNQWQVYANKGKINQYRPYLactococcus garvieae21881[94]
Lactococcin 972MKTKSLVLALSAVTLFSAGGIVAQAEGTWQHGYGVSSAYSNYHHGSKTHSATVVNNNTGRQGKDTQRAGVWAKATVGRNLTEKASFYYNFWLactococcus lactisIPLA 972[95]
Lactococcin AMKNQLNFNIVSDEELSEANGGKLTFIQSTAAGDLYYNTNTHKYVYQQTQNAFGAAANTIVNGWMGGAAGGFGLHHLactococcus lactisLMG 2130[96]
Lactococcin BMKNQLNFNIVSDEELAEVNGGSLQYVMSAGPYTWYKDTRTGKTICKQTIDTASYTFGVMAEGWGKTFHLactococcus lactis9B4[97]
Enterocin BMQNVKELSTKEMKQIIGGENDHRMPNELNRPNNLSKGGAKCGAAIAGGLFGIPKGPLAWAAGLANVYSKCNEnterococcus faeciumT136[98]
Carnobacteriocin AMNNVKELSIKEMQQVTGGDQMSDGVNYGKGSSLSKGGAKCGLGIVGGLATIPSGPLGWLAGAAGVINSCMKCarnobacterium piscicolaLV17A[99]
Gray letters represent leader sequence.
Table 2. Characteristics of the amino acid sequence of class II bacteriocins of LAB.
Table 2. Characteristics of the amino acid sequence of class II bacteriocins of LAB.
BacteriocinNumber of Amino AcidsPIaNet ChargeRatio of Amino Acid GroupMost Enriched Amino AcidsAmino Acids Absent
PolarNon-PolarAromaticAcidicBasic
Class IIa
Acidocin A5810.810.141% (24)24% (14)10% (6)2% (1)22% (13)K(8)G(7)L(7) T(6)ME
Bacteriocin 31439.7440% (17)23% (10)16% (7)5% (2)16% (7)G(5)N(4)W(4)K(4)FM
Bacteriocin BM1438.9247% (20)28% (12)9% (4)5% (2)12% (5)G(7)A(5)I(4)K(4)I(4)PFDR
Bacteriocin B248103.942% (20)38% (18)8% (4)2% (1)10% (5)G(8)S(7)V(5)N(5)LMWDH
Bacteriocin T8449.4341% (18)20% (9)16% (7)7% (3)16% (7)G(6)N(5)K(4)W(4)FMS
Carnobacteriocin B248103.942% (20)35% (17)10% (5)2% (1)10% (5)G(8)S(7)V(5)N(4)LMDH
Carnobacteriocin BM1438.9247% (20)28% (12)9% (4)5% (2)12% (5)G(7)A(5)I(4)N(4)K(4)PFDR
Coagulin448.73.136% (16)36% (16)9% (4)2% (1)16% (7)G(8)T(5)A(4)C(4)K(4)LPFER
Curvacin A419.62.944% (18)34% (14)10% (4)2% (1)10% (4)G(8)A(4)S(4)N(4)PFDH
Divercin V41438.72.847% (20)28% (12)14% (6)2% (1)9% (4)G(10)V(4)C(4)K(4)MFERH
Enterocin A479.13.943% (20)32% (15)9% (4)2% (1)15% (7)G(9)T(6)K(6)A(4)C(4)QWER
Enterocin CRL35439.83.949% (21)28% (12)9% (4)2% (1)12% (5)G(9)A(6)K(5)N(5)EFHMPQR
Enterocin HF43104.949% (21)26% (11)9% (4)2% (1)14% (6)G(10)K(6)A(5)N(5)PMQFERH
Enterocin P448.3145% (20)30% (13)11% (5)5% (2)9% (4)G(8)A(5)Q(5)S(4)PQFD
Enterocin SE-K4439.73.937% (16)23% (10)16% (7)7% (3)16% (7)G(5)V(5)Y(4)K(4)HMP
Leucocin A3792.141% (15)27% (10)16% (6)3% (1)14% (5)G(8)N(4)A(3)V(3)IPMQD
Mesentericin Y1053792.143% (16)27% (10)14% (5)3% (1)14% (5)G(8)A(4)N(4)S(3)PMQD
Mundticin KS439.83.949% (21)28% (12)9% (4)2% (1)12% (5)G(9)A(6)N(5)K(5)PMQFERH
Pediocin PA-1448.73.136% (16)36% (16)9% (4)2% (1)16% (7)G(8)A(4)C(4)N(4)T(4)K(4)LPFER
Piscicolin 126449.52.948% (21)32% (14)9% (4)2% (1)9% (4)G(9)N(7)A(6)K(4)PMQFERH
Plantaricin 423378.73.132% (12)38% (14)14% (5)0% (0)16% (6)G(6)S(5)C(4)K(3)IPMDER
Sakacin A419.62.944% (18)34% (14)10% (4)2% (1)10% (4)G(8)A(4)S(4)N(4)PFDH
Sakacin P4392.144% (19)30% (13)12% (5)2% (1)12% (5)G(9)N(7)A(6)K(3)LPMQFER
Sakacin G387.91.142% (16)37%(14)11% (4)0% (0)11% (4)G(9)N(5)C(4)V(4)IPMFDER
Unbericin A499.5337% (18)41% (20)10% (5)2% (1)10% (5)N(8)G(8)T(5)K(3)DFP
Bacteriocin L-10773710.2351% (19)22% (8)14% (5)3% (1)11% (4)G(6)I(6)N(4)K(3)F(3)CEHSW
Bavaricin MN429.3351% (21)22% (9)15% (6)2% (1)10% (4)G(10)K(4)V(4)W(3)A(3)EFHMR
Bavaricin A398.31.149% (19)31% (12)8% (3)3% (1)10% (4)G(9)N(6)A(6)T(3)EFLMPQR
Lactococcin MMFII377032% (12)32% (12)11% (4)11% (4)14% (5)S(4)K(4)T(3)G(3)N(3)FMQR
Leucocin C4392.137% (16)37% (16)12% (5)2% (1)12% (5)N(8)G(8)K(3)V(3)EFPQR
Mundticin419.52.949% (21)28% (12)9% (4)2% (1)12% (5)G(9)A(6)K(5)N(5)EFHMPQR
Piscicocin VIa449.52.948% (21)32% (14)9% (4)2% (1)9% (4)G(9)N(7)A(6)K(4)EFHMPQR
Plantaricin C19369.9539% (14)33% (12)11% (4)0% (0)17% (6)G(7)K(4)N(3)A(3)DEIMP
plantaricin LPL-1417.10.137% (15)29% (12)12% (5)7% (3)15% (6)G(6)V(4)C(4)H(3)MPQR
Class IIb
ABP-118118α459.11.976% (34)16% (7)4% (2)0% (0)4% (2)G(13)A(7)L(6)V(4)SQYWDEH
118β469.8363% (29)20% (9)9% (4)0% (0)9% (4)G(15)A(5)S(4)I(4)MQDE
Acidocin LF221BLF221B539.73.947% (25)32% (17)9% (5)2% (1)9% (5)G(8)N(6)A(6)S(4)DH
LF221β48103.956% (27)23% (11)13% (6)0% (0)8% (4)G(12)A(8)W(3)T(3)DEHQ
Brevicin 174A174A-β5510.67.958% (32)22% (12)5% (3)0% (0)15% (8)G(16)K(7)V(5)S(4)QWDEH
174A-γ5310.77.155% (29)25% (13)4% (2)0% (0)17% (9)A(11)G(9)K(7)V(3)T(3)FYDER
Carnobacteriocin XYCbnX3310.3252% (17)24% (8)12% (4)3% (1)9% (3)G(6)V(4)K(3)Q(3)CYDRH
CbnY2910.9452% (15)21% (6)7% (2)3% (1)17% (5)A(4)I(4)G(4)K(3)PCWEH
Enterocin XEntXα4092.143% (17)33% (13)10% (4)3% (1)13% (5)G(5)I(4)L(3)K(3)S(3)N(3)ER
EntXβ3710.33.151% (19)11% (4)11% (4)8% (3)19% (7)G(6)I(5)K(4)A(3)CMTE
Enterocin 1071Entα3910.33.144% (17)23% (9)8% (3)8% (3)18% (7)G(4)A(4)N(4)K(4)CT
Entβ3510.4449% (17)14% (5)14% (5)6% (2)17% (6)G(6)K(6)L(3)P(3)N(3)W(3)SCMRH
Gassericin SGasA6411.44.964% (41)20% (13)8% (5)0% (0)8% (5)G(17)A(11)V(5)I(5)DEHMY
GasX53104.947% (25)34% (18)9% (5)0% (0)9% (5)G(9)N(6)A(5)K(4)DEH
Gassericin TGatA5710.2465% (37)16% (9)11% (6)0% (0)9% (5)G(13)A(12)V(6)N(4)DEMQS
GatX48103.956%(27)23% (11)13% (6)0% (0)8% (4)G(13)A(7)N(3)W(3)DEHQ
Mutacin IVnlm A448.3166% (29)20% (9)5% (2)2% (1)7% (3)A(9)G(8)I(4)T(4)DFMNQ
nlm B496−0.957% (28)20% (10)12% (6)4% (2)6% (3)A(9)G(8)V(6)F(3)EMR
Lactococcin GLcnGα3910.64.138% (15)26% (10)8% (3)8% (3)21% (8)G(6)K(4)A(3)V(3)I(3)N(3)LPCFE
LcnGβ3510.2440% (14)6% (2)20% (7)11% (4)23% (8)K(8)G(5)W(4)A(3)I(3)SCMQTRH
Lactococcin QLcnQα3910.85.138% (15)28% (11)8% (3)5% (2)21% (8)G(5)K(5)A(4)V(3)I(3)S(3)Q(3)T(3)LPCTFE
LcnQβ3510.2443% (15)6% (2)17% (6)11% (4)23% (8)K(8)G(6)W(4)A(3)E(3)SCMQTYRH0
Lactocin 705705α339.61.358% (19)18% (6)12% (4)0% (0)12% (4)G(8)A(6)H(3)N(3)CMTDEK
705β3310.34.248% (16)15% (5)12% (4)3% (1)21% (7)G(7)K(4)Y(3)I(3)L(3)VCTWE
Plantaricin NC8PlnC8α2910.34.131% (9)21% (6)24% (7)3% (1)21% (6)L(4)K(4)Y(3)W(3)ICME
PlnC8β3410.45.232% (11)24% (8)18% (6)3% (1)24% (8)K(5)S(4)I(3)Y(3)CMQD
Plantaricin SPlsα2710.43.156% (15)15% (4)15% (4)0% (0)15% (4)A(7)L(4)G(3)K(2)VPSCQDE
Plsβ2610242% (11)15% (4)19% (5)8% (2)15% (4)A(5)K(4)G(3)S(2)PCMTRH
Plantaricin EFPlnE33125.152% (17)15% (5)9% (3)3% (1)21% (7)G(6)R(4)V(4)I(4)CEMPQTW
PlnF3410.63.250% (17)15% (5)15% (5)3% (1)18% (6)A(5)V(5)G(4)S(3)R(3)CELMQT
Plantaricin JKPlnJ2511.4436% (9)12% (3)20% (5)8% (2)24% (6)G(4)R(4)A(3)W(2)K(2)CHMPQTV
PlnK3210.9547% (15)13% (4)13% (4)6% (2)22% (7)G(6)R(5)A(4)Y(3)CHMPQTV
Salivaricin PSalPα459.11.976% (34)16% (7)4% (2)0% (0)4% (2)G(13) A(7)L(6)V(4)DEHQSWY
SalPβ469.12.165% (30)17% (8)9% (4)0% (0)9% (4)G(15)A(6)S(4)I(4)DEMQT
Thermophilin 13ThmA628.3166% (41)15% (9)10% (6)3% (2)6% (4)G(18)A(12)V(3)F(3)EQRT
ThmB438.3172% (31)19% (8)5% (2)0% (0)5% (2)G(13)I(6)A(6)V(4)DEMPRTY
UncharacterizedLSEI_2392424.4−2.855% (23)17% (7)12% (5)10% (4)7% (3)A(9)S(6)G(5)L(4)CMNQRY
LSEI_23934410.6255% (24)23% (10)9% (4)5% (2)9% (4)G(7)L(6)S(5)V(4)CHMY
UncharacterizedLSEI_24054412.2564% (28)23% (10)2% (1)0% (0)11% (5)A(8)G(7)L(4)T(3)DEHMWY
LSEI_2406589.11.964% (37)21% (12)5% (3)3% (2)7% (4)G(16)A(7)I(6)T(5)EHRWY
Class IIc
Carnocyclin A6010.5467% (40)20% (12)3% (2)2% (1)8% (5)A(9)G(9)V(8)I(8)DCHMPRW
Enterocin NKR-5-3B6410.3564% (41)19% (12)6% (4)2% (1)9% (6)A(14)I(9)G(7)T(6)K(6)V(6)PCMQFERH
Enterocin AS-487010.6660% (42)14% (10)6% (4)6% (4)14% (10)A(12)G(9)K(8)V(8)DCHQ
Garvicin ML6010.6560% (36)22% (13)7% (4)2% (1)10% (6)A(15)L(6)G(6)K(6)CEHPR
Leucocyclicin Q6110.22.166% (40)18% (11)5% (3)3% (2)8% (5)A(14)L(9)G(6)I(5)DCFMRY
Lactocyclicin Q6110.32.272% (44)8% (5)7% (4)3% (2)10% (6)A(17)L(7)G(7)V(6)CMFYE
Plantaricyclin A589.91.167% (39)21% (12)5% (3)2% (1)5% (3)A(14)L(9)G(7)V(6)CEMNRY
Plantacyclin B21AG5810.62.167% (39)19% (11)5% (3)2% (1)7% (4)A(12)L(9)G(8)V(6)T(6)CEMNY
Uberolysin7010.1360% (42)20% (14)7% (5)4% (3)9% (6)A(14)I(11)S(7)V(7)CEHMP
Acidocin B587.70.169% (40)14% (8)9% (5)3% (2)5% (3)A(18)L(8)G(7)T(5)CEMN
Butyrivibriocin AR10583.7−262% (36)17% (10)14% (8)5% (3)2% (1)A(13)I(8)G(6)V(5)CHR
Gassericin A587.70.167% (39)16% (9)9% (5)3% (2)5% (3)A(18)L(8)G(7)T(5)CEN
Reutericin 6587.70.167% (39)16% (9)9% (5)3% (2)5% (3)A(18)L(8)G(7)T(5)CEN
Class IId (leaderless bacteriocins)
Bacteriocin LS2419.42.956% (23)20% (8)17% (7)0% (0)7% (3)G(10)A(6)K(3)Y(3)V(3)DEHQR
Enterocin EJ974410.3439% (17)20% (9)18% (8)5% (2)18% (8)K(6)A(5)Y(5)P(4)DCHS
Epidermicin NI015110.78.139% (20)22% (11)18% (9)2% (1)20% (10)K(9)A(6)L(5)I(5)DCPR
Enterocin Q349.83.935% (12)26% (9)15% (5)6% (2)18% (6)K(6)L(3)G(3)A(3)DHRV
LsbB3010.65.140% (12)13% (4)13% (4)7% (2)27% (8)K(5)G(4)A(3)Y(2)CNQ
Lacticin Q5310.6653% (28)17% (9)11% (6)4% (2)15% (8)K(8)A(7)L(6)G(5)V(5)I(5)CEHPRT
Lacticin Z5310.4553% (28)15% (8)11% (6)6% (3)15% (8)K(8)A(7)I(7)G(5)V(5)CHPRT
Lactolisterin BU4310.64.144% (19)16% (7)19% (8)5% (2)16% (7)W(5)G(5)I(4)A(4)R(3)C
Weisselicin Y4210.34.145% (19)19% (8)19% (8)2% (1)14% (6)I(5)G(5)N(4)V(4)K(4)DCT
Weisselicin M4310.24.144% (19)16% (7)14% (6)7% (3)19% (8)V(6)K(6)G(4)W(3)CNP
Enterocin L50L50A4410.56.148% (21)11% (5)16% (7)5% (2)20% (9)I(9)K(8)G(4)A(4)DCRST
L50B4310.76.140% (17)19% (8)16% (7)5% (2)21% (9)K(7)I(6)G(4)Q(4)CNS
Enterocin MR10MR10A4410.56.148% (21)11% (5)16% (7)5% (2)20% (9)I(9)K(8)G(4)A(4)CRST
MR10B4310.76.140% (17)16% (7)19% (8)5% (2)21% (9)K(7)I(6)G(4)F(4)Q(4)CNS
Garvicin KSKS-A3410.7465% (22)9% (3)9% (3)3% (1)15% (5)G(9)K(5)A(4)I(4)DCFHPQRTY
KS-B3410.8574% (25)6% (2)6% (2)0% (0)15% (5)G(11)A(6)I(5)K(5)DCEHNPQRSVW
KS-C3210.7469% (22)6% (2)6% (2)3% (1)16% (5)G(9)A(5)K(5)I(3)L(3)DCHNPQRSY
Class IId (non-pediocin liner bacteriocins)
Bovicin 255569.22.945% (25)23% (13)20% (11)4% (2)9% (5)G(11)Y(7)V(5)A(5)HM
Enterocin 96488.52.938% (18)33% (16)4% (2)8% (4)17% (8)C(5)A(5)S(4)K(4)D(4)EFW
Garvieacin Q509.72.248% (24)22% (11)14% (7)4% (2)12% (6)G(9)V(6)Y(4)N(4)C
Garvicin A4310.2349% (21)30% (13)14% (6)0% (0)7% (3)G(9)N(7)A(4)L(3)Q(3)Y(3)SCDEH
Lactococcin 97266104.430% (20)33% (22)15% (10)5% (3)17% (11)G(8)T(7)S(6)A(6)N(6)CIMP
Lactococcin A549.31.343% (23)31% (17)15% (8)2% (1)9% (5)A(8)G(8)T(6)N(5)CEPR
Lactococcin B479.3230% (14)34% (16)17% (8)6% (3)13% (6)T(8)G(5)Y(4)K(4)N
Enterocin B539.6353% (28)23% (12)6% (3)6% (3)13% (7)G(8)A(8)N(7)L(5)QT
DivergicinA469.82.970% (32)22% (10)2% (1)0% (0)7% (3)G(14)A(6)L(4)K(3)I(3)SYWDERH
Carnobacteriocin A5391.958% (31)26% (14)4% (2)4% (2)8% (4)G(13)S(6)L(5)A(5)FERH
Garvicins A4310.2349% (21)30% (13)14% (6)0% (0)7% (3)G(9)N(7)A(4)L(3)Q(3)SCDEH
Table 3. Distribution of class II bacteriocin in some food associated LAB.
Table 3. Distribution of class II bacteriocin in some food associated LAB.
Species (Number of Strains Analyzed)Percentage of Strains Harbor Class II BcteriocinNumber of Class II Bacteriocins Identified
IIaIIbIIcIIdIIaIIbIIcIId
Carnobacterium divergens (1)00000000
Carnobacterium maltaromaticum (16)43.75%06.25%18.75%12013
Enterococcus faecalis (32)56.25%3.13%3.13%31.25%201110
Enterococcus faecium (30)83.33%46.66%13.33%76.66%3316431
Enterococcus avium (5)00020%0001
Enterococcus gallinarum (10)00030%0005
Enterococcus durans (12)50%25%08.33%10301
Enterococcus casseliflavus (12)08.33%8.33%25%0217
Enterococcus mundtii (16)31.25%0056.25%5009
Enterococcus sulfureus (1)00000000
Lactobacillus acidophilus (18)94.44%100%0100%1720 53
Amylolactobacillus amylotrophicus (1)0.00%0000000
Lentilactobacillus buchneri (5)00000000
Levilactobacillus brevis (26)00011.54%0005
Lacticaseibacillus casei (14)92.86%21.43%0100%153077
Lactococcus chungangensis (1)00000000
Secundilactobacillus collinoides (2)00000000
Loigolactobacillus coryniformis subsp. torquens (1)00000000
Loigolactobacillus coryniformis subsp. coryniformis (3)00000000
Lactobacillus crispatus (22)36.36%50%072.73%1711027
Companilactobacillus crustorum (3)00000000
Lactobacillus delbrueckii subsp. bulgaricus (14)00000000
Lactobacillus delbrueckii subsp. indicus (2)00000000
Lactobacillus delbrueckii subsp. sunkii (1)100%0001000
Lactobacillus delbrueckii subsp. lactis (5)00080%0004
Lactobacillus delbrueckii subsp. delbrueckii (5)00000000
Lapidilactobacillus dextrinicus (1)00000000
Lactobacillus equicursoris (2)00000000
Lactococcus fujiensis (1)00000000
Fructilactobacillus fructivorans (4)00000000
Lactobacillus gasseri (23)39.13%34.78%39.13%52.17%981226
Lactobacillus helveticus (27)00000000
Lactobacillus iners (17)00000000
Lactobacillus johnsonii (22)72.73%54.55%031.82%271207
Apilactobacillus kunkeei (10)00000000
Lacticaseibacillus paracasei (20)100%35%0100%217094
Schleiferilactobacillus perolens (1)00000000
Lactiplantibacillus plantarum (50)080%4%80%072273
Limosilactobacillus reuteri (31)06.45%06.45%0202
Lacticaseibacillus rhamnosus (30)100%20% 100%326076
Furfurilactobacillus rossiae (1)100%00100%1001
Latilactobacillus sakei (25)32%16%056%104020
Ligilactobacillus salivarius (30)0%50%3.33%56.67%016131
Paucilactobacillus vaccinostercus (1)00000000
Lactococcus garvieae (19)005.26%26.32%0017
Lactococcus lactis subsp. cremoris (21)00085.71%00037
Lactococcus lactis subsp. hordniae (2)00000000
Lactococcus lactis subsp. lactis (20)00050%00018
Lactococcus lactis subsp. tructae (1)000100%0004
Lactococcus piscium (4)25%0050%1003
Lactococcus raffinolactis (4)50%025%100%2015
Leuconostoc carnosum (1)00000000
Leuconostoc citreum (9)00000000
Leuconostoc fallax (1)00000000
Leuconostoc gelidum (11)27.27%0072.73%30014
Leuconostoc kimchi (1)000100%0001
Leuconostoc lactis (7)00071.43%0005
Leuconostoc mesenteroides (40)5%0037.50%20017
Leuconostoc pseudomesenteroides (23)00000000
Oenococcus oeni (40)00000000
Pediococcus pentosaceus (12)58.33%008.30%12001
Pediococcus acidilactici (22)4.50%004.50%2001
Pediococcus damnosus (11)100%0018.18%12002
Pediococcus parvulus (1)00000000
Pediococcus inopinatus (2)000100%0002
Streptococcus thermophilus (42)09.52%0100%050189
Weissella confusa (4)00000000
Weissella cibaria (15)00000000
Weissella kandleri (1)00000000
Weissella koreensis (1)00000000
Weissella oryzae (1)00000000
Weissella viridescens (2)00000000
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MDPI and ACS Style

Zhang, T.; Zhang, Y.; Li, L.; Jiang, X.; Chen, Z.; Zhao, F.; Yi, Y. Biosynthesis and Production of Class II Bacteriocins of Food-Associated Lactic Acid Bacteria. Fermentation 2022, 8, 217. https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8050217

AMA Style

Zhang T, Zhang Y, Li L, Jiang X, Chen Z, Zhao F, Yi Y. Biosynthesis and Production of Class II Bacteriocins of Food-Associated Lactic Acid Bacteria. Fermentation. 2022; 8(5):217. https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8050217

Chicago/Turabian Style

Zhang, Tingting, Yu Zhang, Lin Li, Xiuqi Jiang, Zhuo Chen, Fan Zhao, and Yanglei Yi. 2022. "Biosynthesis and Production of Class II Bacteriocins of Food-Associated Lactic Acid Bacteria" Fermentation 8, no. 5: 217. https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8050217

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