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Fermentation
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Production of Pharmaceuticals and Nutraceuticals by Fermentation
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Production of Pharmaceuticals and Nutraceuticals by Fermentation

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Industrial Fermentation".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 20649

Special Issue Editor

Dr. Donatella Cimini

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Guest Editor
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Via Vivaldi, 43 81100 Caserta, Italy
Interests: metabolic engineering; microbial fermentation; microbial glycosaminoglycans (GAGs) and GAG-like polysaccharides; chondroitin; bioprocess development from lab to pilot scale; probiotics; organic acids; waste biomass valorization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmaceuticals and nutraceuticals are important classes of compounds promoting medical and health benefits. Biopharmaceuticals are obtained using biotechnological processes based on the use of living organisms, and due to their complex structure, they need to be produced by biological systems that have an inherent variability; therefore, it is important to develop robust production processes.

Nutraceuticals, on the other hand, are natural molecules (e.g., polysaccharides, polyunsaturated fatty acids, phytochemicals) normally isolated from plants, animals, and microbial sources, in which they are typically present in very low concentrations. Therefore, raw material supply limitation and environmentally unfriendly extractive procedures, often constrain the manufacturing of large quantities of these compounds.

Efforts to overcome these bottlenecks of robust and more sustainable production processes have fostered the use of wild-type or metabolically engineered microbial, plant, and mammalian cells for the establishment of industrial platforms. In order to maximize productivity, strain improvement, media and process design and optimization, and finally scale-up, are crucial aspects.

This Special Issue is inviting manuscripts that describe metabolic engineering and fermentation efforts that enable progress in the production of pharmaceuticals and nutraceuticals.

Dr. Donatella Cimini
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. Fermentation 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 2600 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.

Published Papers (7 papers)

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Research

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15 pages, 2462 KiB  
Article
Extractive Fermentation as A Novel Strategy for High Cell Mass Production of Hetero-Fermentative Probiotic Strain Limosilactobacillus reuteri
by Shanmugaprakasham Selvamani, Solleh Ramli, Daniel Joe Dailin, Khairun Hani Natasya, Theodoros Varzakas, Bassam Abomoelak, Dalia Sukmawati, Muktiningsih Nurjayadi, Siqing Liu, Vijai Kumar Gupta and Hesham Ali El Enshasy
Fermentation 2022, 8(10), 527; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8100527 - 10 Oct 2022
Cited by 3 | Viewed by 2156
Abstract
This study reports on a novel technique to enhance the high cell mass and viable cell counts of the heterofermentative probiotic strain, Limosilactobacillus reuteri. This is the first report on the cultivation of L. reuteri, which was incorporated with weak base [...] Read more.
This study reports on a novel technique to enhance the high cell mass and viable cell counts of the heterofermentative probiotic strain, Limosilactobacillus reuteri. This is the first report on the cultivation of L. reuteri, which was incorporated with weak base anion-exchange resins to remove the accumulating lactic acid in the fermentation broth. Two anion-exchange resins—Amberlite IRA 67 and IRA 96—were found to have a high adsorption capacity with lactic acid. Batch fermentation and fed-batch cultivation were further analyzed using IRA 67 resins, as this application resulted in a higher maximum number of viable cells. The in situ application of anion-exchange resins was found to create shear stress, and thus, it does not promote growth of L. reuteri; therefore, an external and integrated resin column system was proposed. The viable cell count from batch fermentation, when incorporated with the integrated resin column, was improved by 71 times (3.89 × 1011 ± 0.07 CFU mL−1) compared with control batch fermentation (5.35 × 109 ± 0.32 CFU mL−1), without the addition of resins. The growth improvement was achieved due to the high adsorption rate of lactic acid, which was recorded by the integrated IRA 67 resin system, and coupled with the stirred tank bioreactor batch fermentation process. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)
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12 pages, 3591 KiB  
Article
No Waste from Waste: Membrane-Based Fractionation of Second Cheese Whey for Potential Nutraceutical and Cosmeceutical Applications, and as Renewable Substrate for Fermentation Processes Development
by Alberto Alfano, Sergio D’ambrosio, Donatella Cimini, Luca Falco, Maria D’Agostino, Rosario Finamore and Chiara Schiraldi
Fermentation 2022, 8(10), 514; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8100514 - 04 Oct 2022
Cited by 3 | Viewed by 1625
Abstract
Second cheese whey (SCW) derived from buffalo milk is the main by-product of the mozzarella cheese dairy industry. The objective of this study was to develop a membrane-based purification procedure to obtain specific fractions from SCW and assess their biological and applicative potential. [...] Read more.
Second cheese whey (SCW) derived from buffalo milk is the main by-product of the mozzarella cheese dairy industry. The objective of this study was to develop a membrane-based purification procedure to obtain specific fractions from SCW and assess their biological and applicative potential. Special interest was paid to the proteins and newly identified health-promoting compounds that could be recovered and used as value-added products in different sectors of food and pharmaceutical industries. SCW has been treated, sequentially, with microfiltration (MF), ultrafiltration (UF), and nanofiltration (NF) membranes giving the possibility to obtain three different fractions, namely retentates recovered on 100 and 10 kDa (R100 and R10) and a nanofiltration retentate (RNF). These retentates were compared for their ability to preserve human keratinocytes from dehydration, to form protein-based films by casting, and finally they were used for probiotic cultivations as the main substrate. Results showed that Lactobacillus rhamnosus could grow without any further additional nutrient up to 2.2 ± 0.3 × 109 CFU/mL in the RNF medium. Dehydration tests on HaCat cells proved R100 as the most efficient fraction in preserving cell viability from this specific stress. R10, after diafiltrations, formed transparent films with improved features when glycerol was added as a plasticizer. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)
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12 pages, 2332 KiB  
Article
Streptomyces sp. ADR1, Strain Producing β- and γ-Rubromycin Antibiotics, Isolated from Algerian Sahara Desert
by Ali Zineddine Boumehira, Bronywn Kirby, Marla Trindade, Hocine Hacène, Enoch Y. Park and Hesham A. El Enshasy
Fermentation 2022, 8(10), 473; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8100473 - 21 Sep 2022
Cited by 1 | Viewed by 2334
Abstract
A Gram-positive strain, ADR1, was isolated from soil collected from the Algerian Sahara Desert. The ethyl acetate extract of the fermentation broth showed cytotoxic activity against the PANC-1 cell line (37.1 ± 1.3% viability when applied at a concentration of 100 µg/mL). Fractionation [...] Read more.
A Gram-positive strain, ADR1, was isolated from soil collected from the Algerian Sahara Desert. The ethyl acetate extract of the fermentation broth showed cytotoxic activity against the PANC-1 cell line (37.1 ± 1.3% viability when applied at a concentration of 100 µg/mL). Fractionation and NMR analysis of two peaks absorbing at 490 nm revealed that they represented β- and γ-rubromycin, anticancer antibiotic compounds. The ADR1 strain contained LL-diaminopimelic acid in the whole-cell hydrolysate, and the partial 16S ribosomal RNA gene sequence (1392 bp, Accession No. KF947515) showed 99% sequence similarity to Streptomyces species. Therefore, the name Streptomyces sp. ADR1 was proposed and deposited in the Wellness Industries Culture Collection (WICC) of the Institute of Bioproduct Development, UTM, Malaysia, under the number (WICC- B86). In a 16 L stirred-tank bioreactor, the stain was adapted to submerged culture conditions and produced rubromycins at a relatively high concentration, with maximums of 24.58 mg/L and 356 mg/L for β- and γ-rubromycins, respectively. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)
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16 pages, 842 KiB  
Article
Selection and Optimization of Medium Components for the Efficient Production of L-Asparaginase by Leucosporidium scottii L115—A Psychrotolerant Yeast
by Ignacio S. Moguel, Celina K. Yamakawa, Larissa P. Brumano, Adalberto Pessoa, Jr. and Solange I. Mussatto
Fermentation 2022, 8(8), 398; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8080398 - 17 Aug 2022
Cited by 5 | Viewed by 1890
Abstract
This study reports the production of L-asparaginase (ASNase), an enzyme mainly used for the treatment of acute lymphoblastic leukemia, by Leucosporidiumscottii L115, a psychrotolerant yeast isolated from the Antarctic ecosystem. Focus was given to select the most appropriate medium components able to [...] Read more.
This study reports the production of L-asparaginase (ASNase), an enzyme mainly used for the treatment of acute lymphoblastic leukemia, by Leucosporidiumscottii L115, a psychrotolerant yeast isolated from the Antarctic ecosystem. Focus was given to select the most appropriate medium components able to maximize the enzyme production by this yeast, as a first step for the development of a new process to produce ASNase. By combining knowledge in bioprocesses, statistical analysis and modeling, the medium composition that most favored enzyme production was established, which consisted of using a mixture of sucrose (28.34 g L−1) and glycerol (15.61 g L−1) as carbon sources, supplemented with proline (6.15 g L−1) and the following salts (g L−1): KCl, 0.52; MgSO4·7H2O, 0.52; CuNO3·3H2O, 0.001; ZnSO4·7H2O, 0.001; and FeSO4·7H2O, 0.001. By using this medium, enzyme production of 2850 U L−1 (productivity of 23.75 U L−1 h−1) was obtained, which represented a 28-fold increase in enzyme production per gram of cells (178 U gdcw−1) when compared to the control (non-optimized medium), and a 50-fold increase when compared to a reference medium used for ASNase production. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)
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18 pages, 1815 KiB  
Article
Effects of Fermented Camel Milk Supplemented with Sidr Fruit (Ziziphus spina-christi L.) Pulp on Hyperglycemia in Streptozotocin-Induced Diabetic Rats
by El Sayed Hassan Atwaa, Magdy Ramadan Shahein, Barakat M. Alrashdi, Moustafa A. A. Hassan, Mohamed A. Alblihed, Naief Dahran, Fatma Abo Zakaib Ali and Ehab Kotb Elmahallawy
Fermentation 2022, 8(6), 269; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8060269 - 08 Jun 2022
Cited by 6 | Viewed by 2914
Abstract
Diabetes is one of the most common chronic metabolic diseases, and its occurrence rate has increased in recent decades. Sidr (Ziziphus spina-christi L.) is a traditional herbaceous medicinal plant. In addition to its good flavor, sidr has antidiabetic, anti-inflammatory, sedative, analgesic, and [...] Read more.
Diabetes is one of the most common chronic metabolic diseases, and its occurrence rate has increased in recent decades. Sidr (Ziziphus spina-christi L.) is a traditional herbaceous medicinal plant. In addition to its good flavor, sidr has antidiabetic, anti-inflammatory, sedative, analgesic, and hypoglycemic activities. Camel milk has a high nutritional and health value, but its salty taste remains the main drawback in relation to its organoleptic properties. The production of flavored or fortified camel milk products to mask the salty taste can be very beneficial. This study aimed to investigate the effects of sidr fruit pulp (SFP) on the functional and nutritional properties of fermented camel milk. SFP was added to camel milk at rates of 5%, 10%, and 15%, followed by the selection of the best-fermented product in terms of functional and nutritional properties (camel milk supplemented with 15% SFP), and an evaluation of its hypoglycemic activity in streptozotocin (STZ)-induced diabetic rats. Thirty-two male adult albino rats (weighing 150–185 g) were divided into four groups: Group 1, nontreated nondiabetic rats (negative control); Group 2, diabetic rats given STZ (60 mg/kg body weight; positive control); Group 3, diabetic rats fed a basal diet with fermented camel milk (10 g/day); and Group 4, diabetic rats fed a basal diet with fermented camel milk supplemented with 15% SFP (10 g/day). The results revealed that supplementation of camel milk with SFP increased its total solids, protein, ash, fiber, viscosity, phenolic content, and antioxidant activity, which was proportional to the supplementation ratio. Fermented camel milk supplemented with 15% SFP had the highest scores for sensory properties compared to other treatments. Fermented camel milk supplemented with 15% SFP showed significantly decreased (p < 0.05) blood glucose, malondialdehyde, low-density lipoprotein-cholesterol, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, creatinine, and urea, and a significantly increased (p < 0.05) high-density lipoprotein-cholesterol, total protein content, and albumin compared to diabetic rats. The administration of fermented camel milk supplemented with 15% SFP in diabetic rats restored a series of histopathological changes alonsgside an improvement in various enzyme and liver function tests compared to the untreated group, indicating that fermented camel milk supplemented with 15% SFP might play a preventive role in such patients. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)
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13 pages, 316 KiB  
Article
Production of a Yogurt Drink Enriched with Golden Berry (Physalispubescens L.) Juice and Its Therapeutic Effect on Hepatitis in Rats
by Magdy Ramadan Shahein, El Sayed Hassan Atwaa, Hanan A. Radwan, Abdelmoneim Ahmed Elmeligy, Amin A. Hafiz, Ashraf Albrakati and Ehab Kotb Elmahallawy
Fermentation 2022, 8(3), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8030112 - 06 Mar 2022
Cited by 16 | Viewed by 3502
Abstract
Fermented dairy products have been associated with multiple health benefits. The present study aimed to produce a functional yogurt drink fortified with golden berry juice and assess its therapeutic effect on hepatitis rats. Thirty male albino rats were randomly divided into two major [...] Read more.
Fermented dairy products have been associated with multiple health benefits. The present study aimed to produce a functional yogurt drink fortified with golden berry juice and assess its therapeutic effect on hepatitis rats. Thirty male albino rats were randomly divided into two major groups. The first group included the control (-) animals (six rats) and was fed a standard diet, whereas the second group included 24 rats that were fed a standard diet and injected with carbon tetrachloride (CCl4) for 2 weeks to trigger chronic damage of the liver (hepatitis); they were then divided into four groups (six rats/group): Group 2: hepatitis, fed on a standard diet as a positive control group; Group 3: received a basal diet with 5 mL of the yogurt drink; Group 4: received a basal diet with 5 mL of the yogurt drink fortified with 10% golden berry juice. Group 5: received a basal diet with 5 mL of the yogurt drink fortified with 20% golden berry juice. Various biological parameters were determined. Yogurt drink treatments were evaluated for their chemical, phytochemical, and sensory properties, as well as for their effects on hepatoprotective activity by determining various biochemical parameters. We found that the yogurt drinks containing golden berry juice exhibited no significant differences in fat, protein, and ash content compared with the control samples. Moreover, the yogurt drinks containing golden berry juice exhibited the highest content of total phenolic compounds, antioxidant activity, and organoleptic scores among all treatments. In addition, rats fed on a diet fortified with yogurt drinks containing golden berry juice for 8 weeks exhibited higher potential hepatoprotective effects compared with the liver injury control group. This improvement was partly observed in the group that received the yogurt drink containing golden berry juice. Therefore, we concluded that golden berry juice can be recommended as a natural additive in the manufacture of functional yogurt drinks, as it showed a potential hepatoprotective effect in rats with hepatitis. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)

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11 pages, 729 KiB  
Review
Chondroitin Sulfate and Its Derivatives: A Review of Microbial and Other Production Methods
by Adeola E. Awofiranye, Jon Hudson, Aditi Dey Tithi, Robert J. Linhardt, Wanwipa Vongsangnak and Mattheos A. G. Koffas
Fermentation 2022, 8(7), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/fermentation8070323 - 10 Jul 2022
Cited by 9 | Viewed by 5029
Abstract
Chondroitin sulfate (CS) is widely used across the world as a nutraceutical and pharmaceutical. Its high demand and potential limitations in current methods of extraction call for an alternative method of production. This review highlights glycosaminoglycan’s structure, its medical significance, animal extraction source, [...] Read more.
Chondroitin sulfate (CS) is widely used across the world as a nutraceutical and pharmaceutical. Its high demand and potential limitations in current methods of extraction call for an alternative method of production. This review highlights glycosaminoglycan’s structure, its medical significance, animal extraction source, and the disadvantages of the extraction process. We cover alternative production strategies for CS and its precursor, chondroitin. We highlight chemical synthesis, chemoenzymatic synthesis, and extensively discuss how strains have been successfully metabolically engineered to synthesize chondroitin and chondroitin sulfate. We present microbial engineering as the best option for modern chondroitin and CS production. We also explore the biosynthetic pathway for chondroitin production in multiple microbes such as Escherichia coli, Bacillus subtilis, and Corynebacterium glutamicum. Lastly, we outline how the manipulation of pathway genes has led to the biosynthesis of chondroitin derivatives. Full article
(This article belongs to the Special Issue Production of Pharmaceuticals and Nutraceuticals by Fermentation)
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