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Antibiotics
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Discovery and Biosynthesis of Novel Antibiotic from Streptomyces
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Discovery and Biosynthesis of Novel Antibiotic from Streptomyces

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "The Global Need for Effective Antibiotics".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 16584

Special Issue Editor

Dr. Olga Sekurova

E-Mail Website
Guest Editor
Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Vienna, Austria
Interests: bacterial genetics and genomics; secondary metabolite biosynthesis; metabolic engineering; synthetic biology

Special Issue Information

Dear Colleagues,

Streptomyces species are well-known industrial bacteria that produce about two-thirds of all medically important secondary metabolites, including compounds of diverse classes of antibiotics.

Unfortunately, during the last 20 years, very few new antibiotics from Streptomyces or other organisms have been detected due to the re-discovery of known compounds, limited abilities to cultivate newly founded species, or narrow knowledge on the regulation and biosynthesis of secondary metabolites. The discovery of novel antibiotics is of great importance due to the increasing number of multi-resistant microbial pathogens, as a result of the uncontrolled application of antibiotics in medicine and agriculture.

Analyses of the genomes of many Streptomyces have revealed that each can contain 20–50 or more biosynthetic gene clusters and many encoded products, which are not associated with any known natural compounds, and, thus, are a real gold mine for the discovery of new potential antibiotics.

This Special Issue will highlight recent developments in genome-based methods and strategies focused on the discovery, analysis, and manipulation of structural and regulatory genes in “orphan” biosynthetic gene clusters, to activate or increase the production of valuable compounds, and also the heterologous expression and application of synthetic biology tools for the discovery of novel antibiotics from Streptomyces. Manuscripts that further our understanding of recent advances in the field of antimicrobial drug discovery from other Actinomycetes are also welcome.

Dr. Olga Sekurova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibiotics
  • Streptomyces
  • Actinomycetes
  • Biosynthetic pathway
  • Orphan gene clusters
  • Heterologous expression
  • Synthetic biology

Published Papers (5 papers)

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Research

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14 pages, 2902 KiB  
Article
Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data from Both Streptomyces ansochromogenes and ΔwblA
by Yue Li, Haiying Yu, Hanye Guan, Jingjing Li, Jihui Zhang, Hua Xiang, Jine Li and Huarong Tan
Antibiotics 2021, 10(9), 1097; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10091097 - 10 Sep 2021
Cited by 4 | Viewed by 2280
Abstract
With the increase of drug resistance caused by the improper use and abuse of antibiotics, human beings are facing a global health crisis. Sequencing of Streptomyces genomes revealed the presence of an important reservoir of secondary metabolic gene clusters for previously unsuspected products [...] Read more.
With the increase of drug resistance caused by the improper use and abuse of antibiotics, human beings are facing a global health crisis. Sequencing of Streptomyces genomes revealed the presence of an important reservoir of secondary metabolic gene clusters for previously unsuspected products with potentially valuable bioactivity. It has therefore become necessary to activate these cryptic pathways through various strategies. Here, we used RNA-seq data to perform a comparative transcriptome analysis of Streptomyces ansochromogenes (wild-type, WT) and its global regulatory gene disruption mutant ΔwblA, in which some differentially expressed genes are associated with the abolished nikkomycin biosynthesis and activated tylosin analogue compounds (TACs) production, and also with the oviedomycin production that is induced by the genetic manipulation of two differentially expressed genes (san7324 and san7324L) encoding RsbR. These results provide a significant clue for the discovery of new drug candidates and the activation of cryptic biosynthetic gene clusters. Full article
(This article belongs to the Special Issue Discovery and Biosynthesis of Novel Antibiotic from Streptomyces)
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16 pages, 3642 KiB  
Article
Biosynthesis and Heterologous Expression of Cacaoidin, the First Member of the Lanthidin Family of RiPPs
by Fernando Román-Hurtado, Marina Sánchez-Hidalgo, Jesús Martín, Francisco Javier Ortiz-López and Olga Genilloud
Antibiotics 2021, 10(4), 403; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040403 - 08 Apr 2021
Cited by 19 | Viewed by 4328
Abstract
Cacaoidin is produced by the strain Streptomyces cacaoi CA-170360 and represents the first member of the new lanthidin (class V lanthipeptides) RiPP family. In this work, we describe the complete identification, cloning and heterologous expression of the cacaoidin biosynthetic gene cluster, which shows [...] Read more.
Cacaoidin is produced by the strain Streptomyces cacaoi CA-170360 and represents the first member of the new lanthidin (class V lanthipeptides) RiPP family. In this work, we describe the complete identification, cloning and heterologous expression of the cacaoidin biosynthetic gene cluster, which shows unique RiPP genes whose functions were not predicted by any bioinformatic tool. We also describe that the cacaoidin pathway is restricted to strains of the subspecies Streptomyces cacaoi subsp. cacaoi found in public genome databases, where we have also identified the presence of other putative class V lanthipeptide pathways. This is the first report on the heterologous production of a class V lanthipeptide. Full article
(This article belongs to the Special Issue Discovery and Biosynthesis of Novel Antibiotic from Streptomyces)
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13 pages, 1201 KiB  
Article
Amycolatomycins A and B, Cyclic Hexapeptides Isolated from an Amycolatopsis sp. 195334CR
by Gian Primahana, Chandra Risdian, Tjandrawati Mozef, Joachim Wink, Frank Surup and Marc Stadler
Antibiotics 2021, 10(3), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030261 - 05 Mar 2021
Cited by 7 | Viewed by 2303
Abstract
The rare actinobacterium Amycolatopsis sp. strain 195334CR was found to produce previously undescribed cyclic hexapeptides, which we named amycolatomycin A and B (1 and 2). Their planar structures were determined by high-resolution mass spectrometry as well as extensive 1D and 2D [...] Read more.
The rare actinobacterium Amycolatopsis sp. strain 195334CR was found to produce previously undescribed cyclic hexapeptides, which we named amycolatomycin A and B (1 and 2). Their planar structures were determined by high-resolution mass spectrometry as well as extensive 1D and 2D NMR spectroscopy, while the absolute stereochemistry of its amino acids were determined by Marfey’s method. Moreover, 1 and 2 differ by the incorporation of l-Ile and l-allo-Ile, respectively, whose FDVA (Nα-(2,4-Dinitro-5-fluorphenyl)-L-valinamide) derivatives were separated on a C4 column. Their hallmark in common is a unique 2,6-dichloro-tryptophan amino acid unit. Amycolatomycin A (1) exhibited weak activity against Bacillus subtilis DSM 10 (minimum inhibitory concentration (MIC) = 33.4 µg/mL). Full article
(This article belongs to the Special Issue Discovery and Biosynthesis of Novel Antibiotic from Streptomyces)
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Review

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32 pages, 9881 KiB  
Review
New Glycosylated Polyene Macrolides: Refining the Ore from Genome Mining
by Patrick Caffrey, Mark Hogan and Yuhao Song
Antibiotics 2022, 11(3), 334; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030334 - 03 Mar 2022
Cited by 8 | Viewed by 3746
Abstract
Glycosylated polyene macrolides include effective antifungal agents, such as pimaricin, nystatin, candicidin, and amphotericin B. For the treatment of systemic mycoses, amphotericin B has been described as a gold-standard antibiotic because of its potent activity against a broad spectrum of fungal pathogens, which [...] Read more.
Glycosylated polyene macrolides include effective antifungal agents, such as pimaricin, nystatin, candicidin, and amphotericin B. For the treatment of systemic mycoses, amphotericin B has been described as a gold-standard antibiotic because of its potent activity against a broad spectrum of fungal pathogens, which do not readily become resistant. However, amphotericin B has severe toxic side effects, and the development of safer alternatives remains an important objective. One approach towards obtaining such compounds is to discover new related natural products. Advances in next-generation sequencing have delivered a wealth of microbial genome sequences containing polyene biosynthetic gene clusters. These typically encode a modular polyketide synthase that catalyzes the assembly of the aglycone core, a cytochrome P450 that oxidizes a methyl branch to a carboxyl group, and additional enzymes for synthesis and attachment of a single mycosamine sugar residue. In some cases, further P450s catalyze epoxide formation or hydroxylation within the macrolactone. Bioinformatic analyses have identified over 250 of these clusters. Some are predicted to encode potentially valuable new polyenes that have not been uncovered by traditional screening methods. Recent experimental studies have characterized polyenes with new polyketide backbones, previously unknown late oxygenations, and additional sugar residues that increase water-solubility and reduce hemolytic activity. Here we review these studies and assess how this new knowledge can help to prioritize silent polyene clusters for further investigation. This approach should improve the chances of discovering better antifungal antibiotics. Full article
(This article belongs to the Special Issue Discovery and Biosynthesis of Novel Antibiotic from Streptomyces)
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Other

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8 pages, 677 KiB  
Perspective
Biosynthetic Potential of Streptomyces Rationalizes Genome-Based Bioprospecting
by Balasubramanian Cibichakravarthy and Polapass Arul Jose
Antibiotics 2021, 10(7), 873; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070873 - 19 Jul 2021
Cited by 4 | Viewed by 2716
Abstract
Streptomyces are the most prolific source of structurally diverse microbial natural products. Advancing genome-based analysis reveals the previously unseen potential of Streptomyces to produce numerous novel secondary metabolites, which allows us to take natural product discovery to the next phase. However, at present [...] Read more.
Streptomyces are the most prolific source of structurally diverse microbial natural products. Advancing genome-based analysis reveals the previously unseen potential of Streptomyces to produce numerous novel secondary metabolites, which allows us to take natural product discovery to the next phase. However, at present there is a huge disproportion between the rate of genome reports and discovery of new compounds. From this perspective of harnessing the enduring importance of Streptomyces, we discuss the recent genome-directed advancements inspired by hidden biosynthetic wealth that provide hope for future antibiotics. Full article
(This article belongs to the Special Issue Discovery and Biosynthesis of Novel Antibiotic from Streptomyces)
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