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Fermentation
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Microbial Cell Factories for the Production of Functional Compounds
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Microbial Cell Factories for the Production of Functional Compounds

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

Deadline for manuscript submissions: 15 July 2025 | Viewed by 4080

Special Issue Editor

Dr. Nobuhiro Aburai

E-Mail Website
Guest Editor
Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1 Nakano-machi, Hachioji 192-0015, Tokyo, Japan
Interests: secondary metabolites; natural product chemistry; functional compounds; biosynthesis

Special Issue Information

Dear Colleagues,

There is a demand for an industry that is sustainable and places less of a burden on the Earth’s environment, and a paradigm shift is gradually taking place from the era of the mass consumption of fossil fuels to the era of biomass utilization in order to reduce CO2 emissions into the atmosphere. In order to counter environmental and energy issues, the chemical industry, which relies on fossil fuels, is undergoing technological innovation to an industry that uses microorganisms themselves and their biocatalysts. In addition, as the utilization of functional compounds in functional foods, cosmetic materials, pharmaceutical materials, etc., expands, fermentation production and microbial conversion of functional compounds by microorganisms are becoming increasingly important. As mentioned above, functional compounds that are useful in industry are extremely diverse, ranging from inexpensive raw materials that are consumed in large quantities, such as diesel and gasoline, to commoditized chemical products and pharmaceuticals with complex chemical structures. It is an urgent task to break away from the traditional dependence on fossil fuels such as coal, crude oil and natural gas, and there is a strong need to develop production technologies that use biomass as a raw material and utilize the metabolism of microorganisms.

This Special Issue focuses on the current trend and welcomes research related to the culture and microbial conversion techniques used in microbial production of various functional compounds, such as biofuels, functional foods, cosmetic materials and pharmaceutical materials, as well as the metabolic/physiological characterization of microorganisms. In this case, both primary and secondary metabolisms are welcome, as long as the metabolites are functional.

Dr. Nobuhiro Aburai
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 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

  • lipid production
  • peptide production
  • carbohydrate production
  • secondary metabolite
  • bioactive compound
  • biosynthesis
  • photosynthesis
  • respiration
  • fermentation
  • microbial conversion

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Published Papers (3 papers)

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12 pages, 5962 KiB  
Article
Metabolic Engineering of Escherichia coli Nissle 1917 for the Production of Heparosan Using Mixed Carbon Sources
by Fangqi Shao, Ruiji Wu and Zheng-Jun Li
Fermentation 2025, 11(5), 289; https://doi.org/10.3390/fermentation11050289 - 16 May 2025
Viewed by 204
Abstract
Heparosan, a microbially synthesized capsular polysaccharide, possesses a polysaccharide backbone structurally analogous to heparin. Its biosynthesis holds significant importance for achieving the chemoenzymatic synthesis of heparin. Here, we developed a systematic metabolic engineering strategy in Escherichia coli Nissle 1917 to establish an efficient [...] Read more.
Heparosan, a microbially synthesized capsular polysaccharide, possesses a polysaccharide backbone structurally analogous to heparin. Its biosynthesis holds significant importance for achieving the chemoenzymatic synthesis of heparin. Here, we developed a systematic metabolic engineering strategy in Escherichia coli Nissle 1917 to establish an efficient heparosan production platform. Through the systematic engineering of the glycolytic pathway involving the targeted knockout of zwf, pfkAB, pgi, and fruA (or alternatively fbaA) genes, we generated recombinant strains that lost the capacity to utilize glucose or fructose as sole carbon sources in a minimal medium. This metabolic reprogramming established glycerol as the exclusive carbon source for cell growth, thereby creating a tripartite carbon allocation system, including glycerol for biomass, glucose for UDP-glucuronic acid, and fructose for UDP-N-acetylglucosamine. Therefore, heparosan production was significantly improved from 137.68 mg/L in the wild type to 414.40 mg/L in the recombinant strain. Building upon this foundation, the overexpression of glmM, pgm, and galU genes in the biosynthetic pathway enabled a heparosan titer of 773.78 mg/L in shake-flask cultures. Temporal induction optimization further enhanced titers to 1049.96 mg/L, representing a 7.60-fold enhancement compared to the wild-type strain. This study establishes a triple-carbon-source co-utilization strategy, which holds promising implications for the biosynthesis of heparosan-like microbial polysaccharides. Full article
(This article belongs to the Special Issue Microbial Cell Factories for the Production of Functional Compounds)
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12 pages, 1820 KiB  
Article
Metabolic Engineering of Escherichia coli for Xylitol Production
by Jiapeng Li, Lei Zhang, Changzheng Li, Zhaoqing He, Xiongying Yan and Shihui Yang
Fermentation 2025, 11(3), 131; https://doi.org/10.3390/fermentation11030131 - 7 Mar 2025
Viewed by 970
Abstract
Xylitol is a sugar–alcohol compound with broad applications in fields such as the food, dental, and pharmaceutical sectors. Although xylitol biosynthesis has gained attention, the current strategy for industrial xylitol production majorly relies on the chemical hydrogenation of xylose, which is energy-intensive and [...] Read more.
Xylitol is a sugar–alcohol compound with broad applications in fields such as the food, dental, and pharmaceutical sectors. Although xylitol biosynthesis has gained attention, the current strategy for industrial xylitol production majorly relies on the chemical hydrogenation of xylose, which is energy-intensive and environmentally harmful. In this study, the toxicity of xylitol toward Escherichia coli was first examined, and the result demonstrated that Escherichia coli is robust against xylitol at 150 g/L. Genes encoding xylose reductases from different microorganisms were then selected and compared for xylitol production in different E. coli strains. The introduction of xylose reductase of Zymomonas mobilis, driven by the constitutive strong promoter Pgap or Pgap-6M into E. coli, resulted in the accumulation of xylitol at a titer of 64.1 g/L. The increase in NADPH by overexpressing the soluble pyridine nucleotide transhydrogenase encoded by sthA improved the xylitol titer to 83.5 g/L. Seven genes encoding xylose transporters, such as XylE and XylFGH, as well as five mutants of the xylose symporter Glf were then overexpressed and compared for xylitol production. Mutant glfL445I exhibited the highest improvement in xylitol production at a titer of 88.4 ± 0.7 g/L and a yield of 0.95 g/g. Our study thus demonstrated that xylose reductase derived from Z. mobilis is the best one for xylitol production in E. coli, and xylitol production can be further improved by combining diverse metabolic engineering strategies. Our study, thus, provides efficient xylose reductase and a recombinant strain for future industrial xylitol production. Full article
(This article belongs to the Special Issue Microbial Cell Factories for the Production of Functional Compounds)
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16 pages, 2388 KiB  
Article
Efficient Biosynthesis of Ectoine in Recombinant Escherichia coli by Biobrick Method
by Muhammad Naeem, Huiling Yuan, Suya Luo, Simei Zhang, Xinyue Wei, Guangzheng He, Baohua Zhao and Jiansong Ju
Fermentation 2024, 10(9), 450; https://doi.org/10.3390/fermentation10090450 - 29 Aug 2024
Viewed by 2157
Abstract
Ectoine is a compatible solute naturally produced in some halophilic bacteria as a protective agent for survival in salty environments. It has gained special interest as a therapeutic agent in the pharmaceutical and healthcare sectors for the treatment of different diseases. Ectoine mainly [...] Read more.
Ectoine is a compatible solute naturally produced in some halophilic bacteria as a protective agent for survival in salty environments. It has gained special interest as a therapeutic agent in the pharmaceutical and healthcare sectors for the treatment of different diseases. Ectoine mainly produced by bacterial milking, chemical, and fed-batch fermentation methods under a high-salt medium. Unfortunately, the ectoine yield through these methods is still too low to meet high industrial demand, causing salinity issues. The biobrick method was potentially utilized for efficient ectoine biosynthesis under a low-salt medium with different conditions in E. coli BL21(DE3) harboring the pET-22bNS-EctA-EctB-EctC plasmid. Firstly, three genes, L-2,4-diamino-butyric acid acetyltransferase (ectA), L-2,4-diaminobutyric acid transaminase (ectB), and ectoine synthase (ectC) from Bacillus pseudofirmus OF4, were precisely assembled and expressed into E. coli BL21(DE3). After optimizing the reaction conditions in a whole-cell catalytic reaction [50 mM of the sodium phosphate buffer (pH~7.5) containing 300 mM L-aspartic acid, 100 mM glycerol, 1/20 g/mL cell pellets], the amount of ectoine in the plasmid pET-22bNS-ALacBTacCTac reached the maximum level of 167.2 mg/mL/d (6.97 mg/mL/h). Moreover, Western blot analysis revealed that high expression levels of EctA and EctC had a significant effect on ectoine biosynthesis, indicating that both proteins might be the key enzymes in ectoine production. We conclude that a high amount of ectoine achieved through the biobrick method and efficiently used for different industrial applications. Full article
(This article belongs to the Special Issue Microbial Cell Factories for the Production of Functional Compounds)
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