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Microorganisms
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Advances in Metabolic Engineering of Industrial Microorganisms
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Advances in Metabolic Engineering of Industrial Microorganisms

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 9696

Special Issue Editors

Dr. Shuwen Liu

E-Mail Website
Guest Editor
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Interests: metabolic engineering; synthetic biology; industrial microbiology
Prof. Dr. Shuobo Shi

E-Mail Website
Guest Editor
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
Interests: metabolic engineering; microbial cell factory; synthetic biology; biofuel; genome editing

Special Issue Information

Dear Colleagues,

The field of metabolic engineering has emerged as a cornerstone in the optimization and manipulation of microbial metabolism for the production of valuable compounds, biofuels, and bioproducts. Industrial microorganisms, harnessed for their diverse metabolic capabilities, hold immense potential for driving sustainable bioprocessing and advancing the bio-based economy. This Special Issue aims to highlight the forefront of progress in metabolic engineering strategies applied to industrial microorganisms, showcasing innovative approaches, breakthroughs, and applications that pave the way for more efficient and eco-friendly production processes.

The Special Issue welcomes original research articles, reviews, and perspectives that span a wide spectrum of topics within the realm of the metabolic engineering of industrial microorganisms, including, but not limited to, the following:

  • Rational and synthetic biology approaches for enhancing microbial productivity;
  • Strain improvement and optimization through genetic modification and selection;
  • Directed evolution and adaptive laboratory evolution for enhanced phenotypes;
  • Systems biology-guided metabolic pathway design and optimization;
  • Pathway engineering for the production of biofuels, chemicals, pharmaceuticals, and biomaterials;
  • Novel tools and techniques for fine-tuning metabolic pathways and regulation;
  • Engineering strategies for enhancing strain robustness, stability, and scalability.

We aim to foster interdisciplinary collaboration and catalyze advancements in the metabolic engineering of industrial microorganisms. We encourage researchers and experts to contribute their groundbreaking work to this Special Issue, driving innovation and knowledge dissemination in the dynamic field of metabolic engineering.

Dr. Shuwen Liu
Prof. Dr. Shuobo Shi
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 engineering
  • microbial metabolism
  • industrial microorganisms

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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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16 pages, 3773 KiB  
Article
Improving Geldanamycin Production in Streptomyces geldanamycininus Through UV Mutagenesis of Protoplast
by Yuan Yuan, Lu Yang, Zhikai Fang, Haimin Chen, Fei Sun, Hong Jiang and Jian Zhou
Microorganisms 2025, 13(1), 186; https://doi.org/10.3390/microorganisms13010186 - 17 Jan 2025
Viewed by 1017
Abstract
Geldanamycin, a benzoquinone ansa antibiotic, has been extensively applied in medical, agricultural, and health research areas due to its antitumor, antifungal, herbicidal, and antiradiation effects. In this study, an improvement of geldanamycin production by Streptomyces geldanamycininus FIM18-0592 was first performed by protoplasts combined with [...] Read more.
Geldanamycin, a benzoquinone ansa antibiotic, has been extensively applied in medical, agricultural, and health research areas due to its antitumor, antifungal, herbicidal, and antiradiation effects. In this study, an improvement of geldanamycin production by Streptomyces geldanamycininus FIM18-0592 was first performed by protoplasts combined with UV mutagenesis and ribosome engineering technology, respectively. The results showed that strains induced by UV mutagenesis of protoplasts were superior to protoplasts treated with erythromycin in terms of the positive variability, average relative titer, and maximum relative titer, with values of 51.95%, 99%, and 136%, respectively. A mutant strain that produced 3742 μg/mL geldanamycin was generated by protoplast UV mutagenesis, with a 36% higher yield than the initial strain. Multi-omic analysis revealed that the high-yielding geldanamycin in mutant strain 53 could upregulate GdmG and GdmX by 1.59 and 2.38 times in the ansamycin synthesis pathway, and downregulate pks12, pikAI, and pikAII by 0.25, 0.37, and 0.48 times in the fatty acid synthesis pathway, which was crucial for geldanamycin production. Our study provides a novel S. geldanamycininus geldanamycin production strategy and offers valuable insights for mutagenesis and breeding of other microorganisms. Full article
(This article belongs to the Special Issue Advances in Metabolic Engineering of Industrial Microorganisms)
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20 pages, 8907 KiB  
Article
Proline Improves Pullulan Biosynthesis Under High Sugar Stress Condition
by Keyi Liu, Junqing Wang, Feng Li, Ruiming Wang, Qingming Zeng, Zhenxing Zhang, Hongwei Liu and Piwu Li
Microorganisms 2024, 12(12), 2657; https://doi.org/10.3390/microorganisms12122657 - 21 Dec 2024
Cited by 1 | Viewed by 818
Abstract
Pullulan is an extracellular polysaccharide produced via the fermentation of Aureobasidium pullulans. However, high sugar concentrations and hyperosmotic stress limit pullulan biosynthesis during the fermentation process. Therefore, we investigated the effects of proline supplementation on A. pullulans growth and pullulan biosynthesis [...] Read more.
Pullulan is an extracellular polysaccharide produced via the fermentation of Aureobasidium pullulans. However, high sugar concentrations and hyperosmotic stress limit pullulan biosynthesis during the fermentation process. Therefore, we investigated the effects of proline supplementation on A. pullulans growth and pullulan biosynthesis under high sugar and hyperosmotic stress using physiological, biochemical, and transcriptomic analyses. High sugar concentrations significantly inhibited A. pullulans growth and pullulan biosynthesis. High sugar and hyperosmotic stress conditions significantly increased intracellular proline content in A. pullulans. However, treatment with proline (400 mg/L proline) significantly increased biomass and pullulan yield by 10.75% and 30.06% (174.8 g/L), respectively, compared with those in the control group. To further investigate the effect of proline on the fermentation process, we performed scanning electron microscopy and examined the activities of key fermentation enzymes. Proline treatment preserved cell integrity and upregulated the activities of key enzymes involved in pullulan biosynthesis. Transcriptome analysis revealed that most differentially expressed genes in the proline group were associated with metabolic pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, and sulfur metabolism. Conclusively, proline supplementation protects A. pullulans against high sugar and hyperosmotic stress, providing a new theoretical basis and strategy for the efficient industrial production of pullulans. Full article
(This article belongs to the Special Issue Advances in Metabolic Engineering of Industrial Microorganisms)
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14 pages, 2365 KiB  
Article
Impact of the Deletion of Genes of the Nitrogen Metabolism on Triacylglycerol, Cardiolipin and Actinorhodin Biosynthesis in Streptomyces coelicolor
by Sonia Abreu, Clara Lejeune, Michelle David, Pierre Chaminade and Marie-Joelle Virolle
Microorganisms 2024, 12(8), 1560; https://doi.org/10.3390/microorganisms12081560 - 30 Jul 2024
Viewed by 1362
Abstract
Since nitrogen limitation is known to be an important trigger of triacylglycerol (TAG) accumulation in most microorganisms, we first assessed the global lipid content of 21 strains derived from Streptomyces coelicolor M145 deleted for genes involved in nitrogen metabolism. Seven of these strains [...] Read more.
Since nitrogen limitation is known to be an important trigger of triacylglycerol (TAG) accumulation in most microorganisms, we first assessed the global lipid content of 21 strains derived from Streptomyces coelicolor M145 deleted for genes involved in nitrogen metabolism. Seven of these strains deleted for genes encoding proteins involved in polyamine (GlnA2/SCO2241, GlnA3/SCO6962, GlnA4/SCO1613), or protein (Pup/SCO1646) degradation, in the regulation of nitrogen metabolism (GlnE/SCO2234 and GlnK/SCO5584), or the global regulator DasR/SCO5231 that controls negatively the degradation of N-acetylglucosamine, a constituent of peptidoglycan, had a higher TAG content than the original strain, whereas five of these strains (except the glnA2 and pup mutants) had a lower cardiolipin (CL) content. The production of the blue polyketide actinorhodin (ACT) was totally abolished in the dasR mutant in both Pi conditions, whereas the deletion of pup, glnA2, glnA3, and glnA4 was correlated with a significant increase in total ACT production, but mainly in Pi limitation. Unexpectedly, ACT production was strongly reduced in the glnA3 mutant in Pi proficiency. Altogether, our data suggest that high TAG and ACT biosynthesis and low CL biosynthesis might all contribute to the lowering of oxidative stress resulting from nitrogen limitation or from other causes. Full article
(This article belongs to the Special Issue Advances in Metabolic Engineering of Industrial Microorganisms)
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11 pages, 933 KiB  
Article
An In Vitro Study on the Role of Cellulases and Xylanases of Bacillus subtilis in Dairy Cattle Nutrition
by Valeria Bontà, Marco Battelli, Erlinda Rama, Michela Casanova, Lorenzo Pasotti, Gianluca Galassi, Stefania Colombini and Cinzia Calvio
Microorganisms 2024, 12(2), 300; https://doi.org/10.3390/microorganisms12020300 - 30 Jan 2024
Cited by 3 | Viewed by 2040
Abstract
The administration of Bacilli to dairy cows exerts beneficial effects on dry matter intake, lactation performance, and milk composition, but the rationale behind their efficacy is still poorly understood. In this work, we sought to establish whether cellulases and xylanases, among the enzymes [...] Read more.
The administration of Bacilli to dairy cows exerts beneficial effects on dry matter intake, lactation performance, and milk composition, but the rationale behind their efficacy is still poorly understood. In this work, we sought to establish whether cellulases and xylanases, among the enzymes secreted by B. subtilis, are involved in the positive effect exerted by Bacilli on ruminal performance. We took advantage of two isogenic B. subtilis strains, only differing in the secretion levels of those two enzymes. A multi-factorial study was conducted in which eight feed ingredients were treated in vitro, using ruminal fluid from cannulated cows, with cultures of the two strains conveniently grown in a growth medium based on inexpensive waste. Feed degradability and gas production were assessed. Fiber degradability was 10% higher (p < 0.001) in feeds treated with the enzyme-overexpressing strain than in the untreated control, while the non-overexpressing strain provided a 5% increase. The benefit of the fibrolytic enzymes was maximal for maize silage, the most recalcitrant feed. Gas production also correlated with the amount of enzymes applied (p < 0.05). Our results revealed that B. subtilis cellulases and xylanases effectively contribute to improving forage quality, justifying the use of Bacilli as direct-fed microbials to increase animal productivity. Full article
(This article belongs to the Special Issue Advances in Metabolic Engineering of Industrial Microorganisms)
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Review

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17 pages, 3449 KiB  
Review
Review of the Proteomics and Metabolic Properties of Corynebacterium glutamicum
by Juhwan Park and Sooa Lim
Microorganisms 2024, 12(8), 1681; https://doi.org/10.3390/microorganisms12081681 - 15 Aug 2024
Cited by 1 | Viewed by 3091
Abstract
Corynebacterium glutamicum (C. glutamicum) has become industrially important in producing glutamic acid and lysine since its discovery and has been the subject of proteomics and central carbon metabolism studies. The proteome changes depending on environmental conditions, nutrient availability, and stressors. Post-translational [...] Read more.
Corynebacterium glutamicum (C. glutamicum) has become industrially important in producing glutamic acid and lysine since its discovery and has been the subject of proteomics and central carbon metabolism studies. The proteome changes depending on environmental conditions, nutrient availability, and stressors. Post-translational modification (PTMs), such as phosphorylation, methylation, and glycosylation, alter the function and activity of proteins, allowing them to respond quickly to environmental changes. Proteomics techniques, such as mass spectrometry and two-dimensional gel electrophoresis, have enabled the study of proteomes, identification of proteins, and quantification of the expression levels. Understanding proteomes and central carbon metabolism in microorganisms provides insight into their physiology, ecology, and biotechnological applications, such as biofuels, pharmaceuticals, and industrial enzyme production. Several attempts have been made to create efficient production strains to increase productivity in several research fields, such as genomics and proteomics. In addition to amino acids, C. glutamicum is used to produce vitamins, nucleotides, organic acids, and alcohols, expanding its industrial applications. Considerable information has been accumulated, but recent research has focused on proteomes and central carbon metabolism. The development of genetic engineering technologies, such as CRISPR-Cas9, has improved production efficiency by allowing precise manipulation of the metabolic pathways of C. glutamicum. In addition, methods for designing new metabolic pathways and developing customized strains using synthetic biology technology are gradually expanding. This review is expected to enhance the understanding of C. glutamicum and its industrial potential and help researchers identify research topics and design studies. Full article
(This article belongs to the Special Issue Advances in Metabolic Engineering of Industrial Microorganisms)
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