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Microorganisms
Special Issues
Microbial Manufacture of Natural Products
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Microbial Manufacture of Natural Products

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 3371

Special Issue Editors

Dr. Liang Wang

E-Mail Website
Guest Editor
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China
Interests: microbial metabolism and regulation; metabolic engineering; synthetic biology; fermentation process optimization
Prof. Dr. Xusheng Chen

E-Mail Website
Guest Editor
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China
Interests: natural products biosynthesis; synthetic biology; fermentation process optimization; downstream technologies

Special Issue Information

Dear Colleagues,

The field of microbial manufacture of natural products focuses on harnessing the power of microorganisms to produce a wide range of valuable compounds. Microbial cell factories are extensively employed for the sustainable production of high-value chemicals. With rapid societal progress, humanity faces common pressures related to energy, environment, population, and resources. In recent years, the microbial manufacturing industry has garnered significant attention due to its utilization of renewable raw materials and implementation of clean and efficient processes. There is an enormous demand in various sectors including pharmaceuticals, food, chemical, and energy industries. However, the intricate nature of microbial cell metabolism often results in limited production capacities when synthesizing natural products. The Special Issue "Microbial Manufacture of Natural Products" in Microorganisms presents research on bioproduction pathways and methods utilized by industrial bacteria, actinomycetes, and fungi for producing high-value natural products. It encourages the description of novel biotechnological solutions for metabolite biosynthesis along with their applications in the fields of food/feed processing as well as chemical and medical industries. Studies investigating antimicrobial or bioactive properties of natural products will be given particular consideration within this collection.

1. Systems biology and synthetic biology in the context of cellular manufacturing:

(a) Innovative bacterial biosynthesis of metabolites or antimicrobial bioactive compounds;

(b) Extraction, refinement, and elucidation of the chemical properties of metabolites produced by cellular manufacturing systems.

2. Microbial production processes:

(a) Optimizing the biosynthetic pathways and fermentation process for secondary metabolites, peptides, amino acids, and organic acids;

(b) Exploring alternative biosynthetic strategies as alternatives to chemical synthesis.

Dr. Liang Wang
Prof. Dr. Xusheng Chen
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. Microorganisms 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 2700 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

  • metabolic regulation
  • systems biology
  • synthetic biology
  • optimization of fermentation processes
  • downstream technology

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Published Papers (3 papers)

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Research

21 pages, 599 KiB  
Article
Cocoa Pod Husk Valorization Through Rhizopus stolonifer Solid-State Fermentation: Enhancement in Antioxidant Activity
by Patrick Barros Tiburcio, Dão Pedro de Carvalho Neto, Carlos Ricardo Soccol and Adriane Bianchi Pedroni Medeiros
Microorganisms 2025, 13(4), 716; https://doi.org/10.3390/microorganisms13040716 - 22 Mar 2025
Viewed by 476
Abstract
Cocoa pod husk (CPH), a significant agricultural byproduct of cocoa production, presents an opportunity for sustainable valorization through biotechnological methods. This study aimed to enhance the nutritional, antioxidant, and therapeutic properties of CPH using solid-state fermentation (SSF) with Rhizopus stolonifer. Physicochemical characterization [...] Read more.
Cocoa pod husk (CPH), a significant agricultural byproduct of cocoa production, presents an opportunity for sustainable valorization through biotechnological methods. This study aimed to enhance the nutritional, antioxidant, and therapeutic properties of CPH using solid-state fermentation (SSF) with Rhizopus stolonifer. Physicochemical characterization confirmed CPH’s suitability for SSF, providing a nutrient-rich and favorable environment for fungal growth. The fermentation process significantly improved protein recovery (11.327 ± 0.859 mg g−1) and antioxidant activity, with ORAC (51.68 ± 0.35 mmol TE g−1) and DPPH (7.09 ± 0.05 µmol TE g−1) assays demonstrating marked increases in redox potential, particularly at 144 h and 96 h of fermentation, respectively. GC-MS analysis revealed the generation of bioactive compounds in fermented CPH (CPHF), including methyl 3-hydroxybutyrate, 10,12-Tricosadiynoic acid, and palmitic acid, which are known for their antioxidant, anti-inflammatory, and therapeutic properties. Additionally, phenolic compounds are biotransformed into more bioavailable forms, further enhancing the functional value of the material. This work demonstrates that SSF can effectively transform CPH from an agricultural waste product into a high-value biomaterial with potential applications in functional food, nutraceutical, and pharmaceutical industries. By addressing waste management challenges and promoting the development of innovative bio-based products, this study highlights the promising role of SSF in advancing sustainable and circular biotechnological solutions. Full article
(This article belongs to the Special Issue Microbial Manufacture of Natural Products)
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15 pages, 3129 KiB  
Article
Improved Natamycin Production in Streptomyces gilvosporeus Through Mutagenesis and Enhanced Nitrogen Metabolism
by Liang Wang, Wen Xiao, Hongjian Zhang, Jianhua Zhang and Xusheng Chen
Microorganisms 2025, 13(2), 390; https://doi.org/10.3390/microorganisms13020390 - 10 Feb 2025
Viewed by 997
Abstract
Natamycin is a polyene macrocyclic antibiotic extensively used in food, medical, and agricultural industries. However, its high production cost and low synthetic efficiency fail to meet the growing market demand. Therefore, enhancing the production of natamycin-producing strains is crucial for achieving its industrial-scale [...] Read more.
Natamycin is a polyene macrocyclic antibiotic extensively used in food, medical, and agricultural industries. However, its high production cost and low synthetic efficiency fail to meet the growing market demand. Therefore, enhancing the production of natamycin-producing strains is crucial for achieving its industrial-scale production. This study systematically evaluated 16 mutagenesis methods and identified atmospheric and room temperature plasma mutagenesis combined with 2-deoxyglucose tolerance screening as the optimal strategy for enhancing natamycin production. A high-yield mutant strain, AG-2, was obtained, achieving an 80% increase in natamycin production (1.53 g/L) compared to the original strain. Metabolic analysis revealed that glycolysis and the pentose phosphate pathway were enhanced in AG-2, while the tricarboxylic acid cycle was weakened, significantly increasing the supply of precursors such as acetyl-CoA, methylmalonyl-CoA, and the reducing power of NADPH. Additionally, overexpression of the nitrogen metabolism regulatory gene glnR promoted the supply of glutamate and glutamine, further increasing natamycin production in AG-2 to 1.85 g/L. In a 5 L fermenter, the engineered strain AG-glnR achieved a final natamycin production of 11.50 g/L, 1.67 times higher than the original strain. This study is the first to combine mutagenesis with nitrogen metabolism regulation, effectively enhancing natamycin production and providing a novel approach for the efficient synthesis of other polyene antibiotics. Full article
(This article belongs to the Special Issue Microbial Manufacture of Natural Products)
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15 pages, 3060 KiB  
Article
Rational Design for the Complete Synthesis of Stevioside in Saccharomyces cerevisiae
by Wei Huang, Yongheng Liu, Xiaomei Ma, Cilang Ma, Yuting Jiang and Jianyu Su
Microorganisms 2024, 12(6), 1125; https://doi.org/10.3390/microorganisms12061125 - 31 May 2024
Cited by 1 | Viewed by 1324
Abstract
Stevioside is a secondary metabolite of diterpenoid glycoside production in plants. It has been used as a natural sweetener in various foods because of its high sweetness and low-calorie content. In this study, we constructed a Saccharomyces cerevisiae strain for the complete synthesis [...] Read more.
Stevioside is a secondary metabolite of diterpenoid glycoside production in plants. It has been used as a natural sweetener in various foods because of its high sweetness and low-calorie content. In this study, we constructed a Saccharomyces cerevisiae strain for the complete synthesis of stevioside using a metabolic engineering strategy. Firstly, the synthesis pathway of steviol was modularly constructed in S. cerevisiae BY4742, and the precursor pathway was strengthened. The yield of steviol was used as an indicator to investigate the expression effect of different sources of diterpene synthases under different combinations, and the strains with further improved steviol yield were screened. Secondly, glycosyltransferases were heterologously expressed in this strain to produce stevioside, the sequence of glycosyltransferase expression was optimized, and the uridine diphosphate-glucose (UDP-Glc) supply was enhanced. Finally, the results showed that the strain SST-302III-ST2 produced 164.89 mg/L of stevioside in a shake flask experiment, and the yield of stevioside reached 1104.49 mg/L in an experiment employing a 10 L bioreactor with batch feeding, which was the highest yield reported. We constructed strains with a high production of stevioside, thus laying the foundation for the production of other classes of steviol glycosides and holding good prospects for application and promotion. Full article
(This article belongs to the Special Issue Microbial Manufacture of Natural Products)
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