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Fermentation
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New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition
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New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Microbial Metabolism, Physiology & Genetics".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 5673

Special Issue Editors

Prof. Dr. Penka Petrova

E-Mail Website
Guest Editor
Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
Interests: gene expression; cloning; metagenomics; lactic acid fermentation; heterologous expression; glycoside hydrolase enzymes
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Kaloyan Petrov

E-Mail Website
Guest Editor
Institute of Chemical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria
Interests: biofuels; process optimization; waste substrates utilization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microbial biosynthesis is the foundation of numerous biotechnological processes for producing invaluable chemicals widely used as fuels, platform reagents, pharmaceuticals, and various ingredients in everyday food and cosmetics. Biosynthetic pathways also provide a shortcut to valorizing renewable natural resources and waste compounds and a means for developing a circular economy.

This Special Issue aims to combine the latest research in fermentation processes for the biosynthesis of primary and secondary metabolites by genetically improved microbial strains. The scope extends to low molecular weight compounds such as organic acids and alcohols, natural and recombinant enzymes, and biologically active molecules with a protein or lipopeptide nature. Despite the prevailing opinion that the most stable microbial strains applied in industrial biotechnologies are the wild-type isolates found after prolonged selection, modern approaches to genetic engineering offer vast horizons for improvement. In this way, new or enhanced biochemical pathways could be obtained, by-products could be marginalized, and the tolerance to the final biosynthetic product could be increased.

The present Special Issue provides a forum for cutting-edge research in genomics, mutagenesis, and metabolic/enzyme engineering, aiming to achieve enhanced biosynthesis of final metabolites. The development of biotechnologies for novel metabolites or highly optimized microbial processes for the overproduction of those already available and their synthesis from renewable substrates or waste biomass is also welcomed.

Prof. Dr. Penka Petrova
Prof. Dr. Kaloyan Petrov
Guest Editors

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 2100 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

  • genetic improvement
  • biosynthetic pathways engineering
  • microbial biosynthesis of new metabolites
  • biofuels
  • enzymes production
  • bioactive molecules
  • process optimization

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

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Research

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15 pages, 3194 KiB  
Article
Physiological Function of AtrN in Regulating Intracellular NADPH Levels and the Anti-Reductive Stress Response in Corynebacterium glutamicum
by Guotao Xu, Shuping Tian, Zhihan Gong and Jianzhong Xu
Fermentation 2025, 11(3), 149; https://doi.org/10.3390/fermentation11030149 - 17 Mar 2025
Viewed by 384
Abstract
The regulation of intracellular NADPH levels is currently a hotspot for research into bacterial modification and fermentation process optimization, and Corynebacterium glutamicum, an important industrial microorganism, achieves enhanced L-lysine production by regulating intracellular NADPH levels. In previous studies, transcriptome analysis was performed [...] Read more.
The regulation of intracellular NADPH levels is currently a hotspot for research into bacterial modification and fermentation process optimization, and Corynebacterium glutamicum, an important industrial microorganism, achieves enhanced L-lysine production by regulating intracellular NADPH levels. In previous studies, transcriptome analysis was performed on C. glutamicum with different intracellular NADPH levels. The results showed that the expression level of transcription factor AtrN changed significantly. Moreover, experiments showed that transcription factor AtrN can sense high intracellular levels of NADPH and negatively regulate its synthesis. In this study, we integrated the pntAB gene of Escherichia coli into the genome of C. glutamicum XQ-5, successfully constructing a chassis cell with a high intracellular NADPH level. It was named TQ-1. On this basis, we knocked out and complemented the AtrN in strain TQ-1, resulting in strains TQ-2 and TQ-3, respectively. Then, the changes in cell growth, intracellular redox substances and cell membrane among these three strains were investigated. We found that the growth of TQ-2 was inhibited in the early growth stage and the cell survival rate was decreased because of the high increase in the intracellular NADPH level. In addition, the deletion of the AtrN gene also led to a decrease in the fluidity and an increase in the permeability of the cell membrane. Compared with TQ-1, TQ-3 showed slow growth only in the late growth stage, and the fluidity of its cell membrane was also enhanced. This indicates that AtrN guides the cells to make some adaptive changes to maintain cell growth when facing excessive intracellular reductive stress. This will facilitate future research on how potential upstream regulatory genes regulate AtrN and how AtrN regulates downstream genes to cope with cellular reductive stress. It also provides theoretical guidance for the specific modification of high-yield lysine-producing strains. Full article
(This article belongs to the Special Issue New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition)
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19 pages, 2674 KiB  
Article
Synergistic Optimization of Bacillus subtilis for Efficiently Producing Menaquinone-7 (MK-7) by Atmospheric and Room Temperature Plasma (ARTP) Mutagenesis and Metabolic Engineering
by Meng Li, Jiachang Li, Yufei Li, Xian Zhang and Jianzhong Xu
Fermentation 2025, 11(3), 137; https://doi.org/10.3390/fermentation11030137 - 12 Mar 2025
Viewed by 616
Abstract
Menaquinone-7 (MK-7) plays a crucial role in preventing fractures and certain cardiovascular diseases and is one of the essential vitamins in the human body. In this study, a strain of Bacillus subtilis that produces MK-7 was isolated from commercially available natto fermentation agents, [...] Read more.
Menaquinone-7 (MK-7) plays a crucial role in preventing fractures and certain cardiovascular diseases and is one of the essential vitamins in the human body. In this study, a strain of Bacillus subtilis that produces MK-7 was isolated from commercially available natto fermentation agents, with an MK-7 titer of 75 mg/L. It was named L-5. Firstly, by employing Atmospheric and Room Temperature Plasma (ARTP) mutagenesis technology and protoplast fusion techniques, mutants resistant to 1-hydroxy-2-naphthoic acid (HNA) and diphenylamine (DPA) were obtained, with the titer of MK-7 reaching 196 mg/L. It was named R-8. Based on whole-genome sequencing technology, four mutants involved in the MK-7 synthesis pathway of strain L-5 were identified: 2-succinyl-5-enol-pyruvate-6-hydroxy-3-cyclohexen-1-carboxylic acid, MenD (S249L); (1,4)-dihydroxy-2-naphthalic acid-heptaisoprenyltransferase, MenA (S196L); 1-deoxy-D-xylose-5-phosphate synthetase, Dxs (N60D, Q185H); and hydroxy acid reductive isomerase, Dxr (Q351K). The overexpression of these mutants led to increases in MK-7 production of 19 mg/L, 20 mg/L, 17 mg/L, and 16 mg/L, respectively, compared to the unmutated genes. These mutations have been shown to be effective. To further enhance the production of MK-7, the mutants menD (S249L), menA (S196L), Dxs (N60D, Q185H), and Dxr (Q351K) were co-expressed. The final titer of MK-7 reached 239 mg/L. This study provides theoretical support for the future genetic modification of key enzymes in the MK-7 biosynthetic pathway. Full article
(This article belongs to the Special Issue New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition)
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19 pages, 2931 KiB  
Article
Lipid Production in Streptomyces jeddahensis Is Enhanced by Glucose and Fatty Acid Derivatives, with Temperature Variations Influencing Gene Expression and Biosynthesis
by Pamella Apriliana, Prihardi Kahar, Nova Rachmadona, Witta Kartika Restu, Akihiko Kondo and Chiaki Ogino
Fermentation 2025, 11(2), 45; https://doi.org/10.3390/fermentation11020045 - 21 Jan 2025
Viewed by 1102
Abstract
The potential of Streptomyces jeddahensis for lipid production was investigated, focusing on its ability to utilize various carbon sources under different temperature conditions. Glucose and fatty acid derivatives (sodium hexanoate, sodium octanoate, and sodium decanoate) were tested at 30 °C, 37 °C, and [...] Read more.
The potential of Streptomyces jeddahensis for lipid production was investigated, focusing on its ability to utilize various carbon sources under different temperature conditions. Glucose and fatty acid derivatives (sodium hexanoate, sodium octanoate, and sodium decanoate) were tested at 30 °C, 37 °C, and 45 °C to optimize growth and lipid biosynthesis. The results revealed that 37 °C was the optimal temperature for lipid accumulation, with sodium octanoate leading to the highest lipid content. While growth declined at 45 °C, significant lipid production persisted, indicating an adaptive stress response. Gene expression analysis identified upregulation of key metabolic genes, including STSP_03080 (DGAT) and STSP_67970 (fabD), under thermal stress, highlighting enhanced fatty acid biosynthesis pathways. This study demonstrates the capacity of S. jeddahensis to efficiently convert medium-chain fatty acids into lipids, supporting its use as a sustainable and scalable platform for biodiesel production and other lipid-based industrial applications. Full article
(This article belongs to the Special Issue New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition)
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17 pages, 3627 KiB  
Article
Isolation, Purification and In Vitro Characterization of a Newly Isolated Alkalophilic Phytase Produced by the Halophile Cobetia marina Strain 439 for Use as Animal Food Supplement
by Ivanka Boyadzhieva, Kaloyan Berberov, Nikolina Atanasova, Nikolay Krumov and Lyudmila Kabaivanova
Fermentation 2025, 11(1), 39; https://doi.org/10.3390/fermentation11010039 - 17 Jan 2025
Viewed by 1138
Abstract
Economic development increases and brings about issues such as the secure supply of food in a sustainable way. Phytases are enzymes catalyzing phytate hydrolysis to release phosphorus in an inorganic form. Animal feeds could be supplemented with bacterial phytases to increase their phosphorus [...] Read more.
Economic development increases and brings about issues such as the secure supply of food in a sustainable way. Phytases are enzymes catalyzing phytate hydrolysis to release phosphorus in an inorganic form. Animal feeds could be supplemented with bacterial phytases to increase their phosphorus and micronutrients bioavailability. To the best of our knowledge, this is the first report on the purification and characterization of an alkalophilic phytase from Cobetia marina. The purified newly isolated phytase from the halophilic Cobetia marina strain 439 appears to be appropriate for use as an additive in food and feed processing. Its molecular weight was determined to be 43 kDa by gel filtration and 40 kDa by SDS–polyacrylamide gel electrophoresis. The purified enzyme had maximum activity at pH 8.0 and 45 °C, while at 70 °C, it was 80% and about 50% at 80 °C for 40 min, showing its thermostability. Enzyme activity was retained at a broad pH range from 6.5 to 9.0. The half-life of the phytase of 15 min at pH 10 and 30 min at pH 4.0 was registered. The enzyme was proven to be with high substrate specificity. In addition, the purified phytase showed strong proteolytic tolerance against trypsin and pepsin. The pH profile, its thermostability, and proteolytic tolerance of the studied phytase as a halophilic bacterial product determine it as a unique candidate for application in agriculture, food, and feed industries. Full article
(This article belongs to the Special Issue New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition)
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Review

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27 pages, 1597 KiB  
Review
Microbial Conversion of Inulin to Valuable Products: The Biorefinery Concept
by Lidia Tsigoriyna, Stefan Stefanov, Nadya Armenova, Penka Petrova and Kaloyan Petrov
Fermentation 2024, 10(12), 640; https://doi.org/10.3390/fermentation10120640 - 13 Dec 2024
Cited by 1 | Viewed by 1771
Abstract
The global transition to a sustainable bioeconomy requires the engagement of renewable and cost-effective substrates to obtain valuable bio-based products. Inulin-rich plant materials have promising applications in white biotechnology. This review evaluates the potential of converting inulin through an integrated biorefinery into high-value [...] Read more.
The global transition to a sustainable bioeconomy requires the engagement of renewable and cost-effective substrates to obtain valuable bio-based products. Inulin-rich plant materials have promising applications in white biotechnology. This review evaluates the potential of converting inulin through an integrated biorefinery into high-value products by microbial fermentation. It describes the methods for raw biomass and inulin pretreatment, the possibilities of simultaneous saccharification and fermentation (SSF), and the use of wild-type and genetically modified microbial strains. The bioconversion of inulin enables the efficient synthesis of biofuels such as ethanol, butanol, and 2,3-butanediol and biochemicals such as lactic, citric, and poly-γ-glutamic acid. By analyzing the advances in inulin hydrolysis methods, microbial engineering, and bioprocess optimization approaches, this review highlights the broad applicability of inulin in the biorefinery context as a multifunctional, sustainable substrate, which contributes to the development of the circular economy. Full article
(This article belongs to the Special Issue New Research on Strains Improvement and Microbial Biosynthesis, 2nd Edition)
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