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Production of Nutritional and Functional Properties in Genetically Engineered Microorganisms

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

Deadline for manuscript submissions: 31 May 2024 | Viewed by 7289

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Special Issue Editors

Dr. Guojian Zhang

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Guest Editor

School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Interests: heterologous biosynthesis; bioproducts; natural products; genetic engineering; metabolic engineering; bioprocess

Dr. Fu Yan

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Guest Editor

State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
Interests: heterologous biosynthesis; bioproducts; natural products; genetic engineering; metabolic engineering; bioprocess

Special Issue Information

Dear Colleagues,

Microorganisms play a vital role in modern life, with applications ranging from food fermentation to biofuel to pharmaceutical production. During the past decade, microbial fermentation studies on the production of nutritional and functional properties have reached a higher level of sophistication and wider adoption, along with the rapid development of high-throughput DNA sequencing and genome-editing techniques. These advances have enabled researchers to identify the regulatory mechanisms underlying the overproduction of secondary metabolites and to monitor gene expression during the fermentation cycle, accelerating the rational application of metabolic pathway engineering. For this Special Issue, we invite front-line researchers and authors to submit original research and review articles exploring the production of nutritional and functional properties from genetically engineered microbial strains (including Escherichia coli and Bacillus subtilis, Saccharomyces cerevisiae and Pichia pastoris, Streptomyces coelicolor and Streptomyces lividans, Aspergillus nidulans and Aspergillus oryzae, etc.). Papers on efforts to improve microbial strains and addressing the complex problems of screening, advanced tools and technology used for metabolic pathway rebuilding and fine-tuning, and new strategies for process optimization are especially welcome.

Potential topics include, but are not limited to:

（1）Continuous fermentation;

（2）Fed-batch fermentation;

（3）Random mutation and screening;

（4）Mutagenesis and combinatorial biosynthesis;

（5）Heterologous biosynthesis;

（6）Metabolic engineering;

（7） Yield and characterization of metabolites.

Dr. Guojian Zhang
Dr. Fu Yan
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 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.

Keywords

heterologous biosynthesis
bioproducts
natural products
genetic enineering
metabolic engineering
bioprocess

Published Papers (5 papers)

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Research

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12 pages, 2721 KiB

Open AccessArticle

Enhanced Phycocyanobilin Production in Escherichia coli by Fusion-Expression of Apo-Proteins with Signal Peptides

by Xiaolin Liu, Jing Yu, Qian Che, Tianjiao Zhu, Dehai Li and Guojian Zhang

Fermentation 2023, 9(9), 851; https://doi.org/10.3390/fermentation9090851 - 18 Sep 2023

Viewed by 1264

Abstract

Phycocyanobilin (PCB) is the bioactive chromophore attached to Phycocyanin (PC) that is of special interest for nutraceutical and therapeutic applications. However, the production of PCB from the heterologous host Escherichia coli is still very low. To facilitate subsequent application of PCB, improving its production in microbial hosts is still a challenge to be solved. In this paper, a strategy involving fusion-expression of apo-proteins with signal peptides was adopted to improve PCB production in E. coli. First, we reconstructed the PCB biosynthesis pathway in E. coli and then optimized its culture media. Subsequently, one PC α (CpcA) subunit and one PC β (CpcB) subunit, which can capture free PCB, were introduced and increased the yield of PCB. Finally, CpcA was fused with seven signal peptides to generate recombinant proteins, among which, the signal peptide N20 fused with CpcA protein drastically improved PCB production in E. coli, providing a maximum flask output of 8.47 ± 0.18 mg/L. The results of this study demonstrate that PCB distribution and transporting manners in E. coli could affect the heterologous production efficiency. By fusing apo-proteins with signal peptides, the secretion of phycocyanin was refined and the production of PCB was successfully enhanced by 3.7-fold, compared with the starting strain (1.80 ± 0.12 mg/L). This work provided an alternative method for improving the production of PCB and other phycobilins. Full article

(This article belongs to the Special Issue Production of Nutritional and Functional Properties in Genetically Engineered Microorganisms)

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13 pages, 1717 KiB

Open AccessArticle

Optimization of Milbemycin Component Ratio by Coordinating Acyl-Coenzyme A Supply Pathways in Streptomyces bingchenggensis

by Xue Yang, Pinjiao Jin, Zhuoxu Dong, Yanyan Zhang, Wensheng Xiang and Shanshan Li

Fermentation 2023, 9(6), 555; https://doi.org/10.3390/fermentation9060555 - 10 Jun 2023

Viewed by 1027

Abstract

Milbemycins are a group of macrolide pesticides with great potential in the agricultural field owing to their high insecticidal activity and environmental compatibility. Milbemycin A3 and A4 with high bioactivities are the main components of milbemycin-derived products, which require a component ratio A4:A3 of 2.3- to 4.0-fold. Streptomyces bingchenggensis BC04 is a promising milbemycin producer, whereas the component ratio of its products (A4:A3 of 9.0-fold) could not meet the requirement for industrial production. To address this issue, we reconstructed the precursor biosynthetic pathways to fine tune the supply of different acyl-coenzyme A precursors required for milbemycin biosynthesis. Based on an analysis of the intracellular acyl-coenzyme A precursors, we reconstructed stepwise heterogeneous biosynthetic pathways of extender units for milbemycin biosynthesis. Then, we coordinated the supply of milbemycin biosynthetic starter units with temporal promoters. Thanks to these manipulations, we obtained an engineered strain with 39.5% milbemycin titer improvement to 3417.88 mg/L and a qualified component ratio A4:A3 of 3.3-fold. This work demonstrated that coordinating the precursor supply is a simple and effective approach to optimize the component ratio of A4:A3 in milbemycin fermentation products. Moreover, this strategy might also be useful to construct high-yield strains with optimized component ratios of fermentation products in other Streptomyces. Full article

(This article belongs to the Special Issue Production of Nutritional and Functional Properties in Genetically Engineered Microorganisms)

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14 pages, 2594 KiB

Open AccessArticle

Biosynthesis of Gamma-Aminobutyric Acid by Engineered Clostridium tyrobutyricum Co-Overexpressing Glutamate Decarboxylase and Class I Heat Shock Protein

by Ziyao Liu, Xiaolong Guo, Kaiqun Dai, Jun Feng, Tiantian Zhou, Hongxin Fu and Jufang Wang

Fermentation 2023, 9(5), 445; https://doi.org/10.3390/fermentation9050445 - 08 May 2023

Cited by 2 | Viewed by 1595

Abstract

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system that has a significant beneficial effect on human health. Traditional microbial GABA synthesis requires continuous oxygen supplementation. Here, a new anaerobic platform for GABA production was established with engineered C. tyrobutyricum ATCC 25755, which is considered an ideal anaerobic microbial-cell factory for bioproduction. Glutamate decarboxylase (GAD) and Class I heat-shock proteins were screened and overexpressed, generating an excellent Ct-pMAG strain for monosodium-glutamate (MSG) tolerance and GABA production, with a GABA titer of 14.26 g/L in serum bottles with the mixed substrate of glucose and MSG. Fed-batch fermentation was carried out in a 5 L bioreactor, achieving 35.57 g/L and 122.34 g/L final titers of GABA by applying the pH-free strategy and the pH-control strategy, respectively using MSG. Finally, a two-stage strategy (growth stage and bioconversion stage) was applied using glutamate acid (L-Glu) and glucose as the substrate, obtaining a 400.32 g/L final titer of GABA with a productivity of 36.39 g/L/h. Overall, this study provides an anaerobic-fermentation platform for high-level bio-GABA production. Full article

(This article belongs to the Special Issue Production of Nutritional and Functional Properties in Genetically Engineered Microorganisms)

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15 pages, 3462 KiB

Open AccessArticle

Unveiling the Effect of NCgl0580 Gene Deletion on 5-Aminolevulinic Acid Biosynthesis in Corynebacterium glutamicum

by Jian Wu, Meiru Jiang, Shutian Kong, Kunqiang Hong, Juntao Zhao, Xi Sun, Zhenzhen Cui, Tao Chen and Zhiwen Wang

Fermentation 2023, 9(3), 213; https://doi.org/10.3390/fermentation9030213 - 23 Feb 2023

Cited by 2 | Viewed by 1686

Abstract

5-Aminolevulinic acid (5-ALA) has recently received much attention for its wide applications in medicine and agriculture. In this study, we investigated the effect of NCgl0580 in Corynebacterium glutamicum on 5-ALA biosynthesis as well as its possible mechanism. It was found that the overexpression of NCgl0580 increased 5-ALA production by approximately 53.3%. Interestingly, the knockout of this gene led to an even more significant 2.49-fold increase in 5-ALA production. According to transcriptome analysis and functional validation of phenotype-related targets, the deletion of NCgl0580 brought about considerable changes in the transcript levels of genes involved in central carbon metabolism, leading to fluxes redistribution toward the 5-ALA precursor succinyl-CoA as well as ATP-binding cassette (ABC) transporters affecting 5-ALA biosynthesis. In particular, the positive effects of enhanced sugar transport (by overexpressing NCgl1445 and iolT1), glycolysis (by overexpressing pyk2), iron uptake (by overexpressing afuABC), and phosphate uptake (by overexpressing pstSCAB and ugpQ) on 5-ALA biosynthesis were demonstrated for the first time. Thus, the transcriptional mechanism underlying the effect of NCgl0580 deletion on 5-ALA biosynthesis was elucidated, providing new strategies to regulate the metabolic network of C. glutamicum to achieve a further increase in 5-ALA production. Full article

(This article belongs to the Special Issue Production of Nutritional and Functional Properties in Genetically Engineered Microorganisms)

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Review

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14 pages, 2278 KiB

Open AccessReview

Research Progress in Understanding the Molecular Biology of Cordyceps militaris

by Lihong Wang, Ganghua Li, Xueqin Tian, Yitong Shang, Huanhuan Yan, Lihua Yao and Zhihong Hu

Fermentation 2024, 10(3), 167; https://doi.org/10.3390/fermentation10030167 - 15 Mar 2024

Viewed by 1197

Abstract

Cordyceps militaris (C. militaris) is a valued medicinal fungus that can be traced back thousands of years in traditional Chinese medicine (TCM). Both TCM and modern scientific research have confirmed the positive effects of C. militaris on human health. In recent years, C. militaris has gained wide popularity; unfortunately, strains often degrade during cultivation, resulting in a decline in fruiting bodies and active components that negatively impacts the development of C. militaris in the health food and medicine industries. This review summarizes the current progresses in research on the genomic, transcriptomic, proteomic, and genetic manipulation of C. militaris and discusses its primary metabolites and strain degradation mechanisms. The current challenges and future prospects of C. militaris research are also discussed. Full article

(This article belongs to the Special Issue Production of Nutritional and Functional Properties in Genetically Engineered Microorganisms)

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