Construction of High-Efficiency Production Strains by Synthetic Biology and Metabolic Engineering

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Microbiology and Ecological Metabolomics".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 3722

Special Issue Editors

College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China
Interests: metabolic engineering; escherichia coli; corynebacterium glutamicum; amino acids; nucleosides; vatmins
School of Biotechnology, Jiangnan University, Wuxi, China
Interests: protein engineering; cell metabolism; fermentation process; enzymaticization; fermentation control
The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain), Technical University of Denmark, Lyngby, Denmark
Interests: synthetic biology; metabolic engineering; one carbon biotransformation; lipid metabolism; biomass refinery; biofuel; aromatic natural product; yarrowia lipolytic
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark
Interests: synthetic biology; metabolic engineering; microbial communities; lipid metabolism; biomass biorefinery; biofuel; yeast; biosensors; natural product

Special Issue Information

Dear Colleagues,

Bio-economy-derived carbon neutrality has attracted lots of interest internationally due to the advantages of addressing the issues of climate change and global warming. Microbial cell factories, as one of the key components of bio-economy, could be driven by the enabling technologies of synthetic biology and metabolic engineering. Although there have been rapid renovations of synthetic biology tools such as CRISPR genome-editing tools, genetic encoded biosensors, modular gene assembly toolkits, artificial intelligence and machine-learning-guided genome-scale metabolic models, etc., in the last two decades, it is still challenging to employ these tools more efficiently for strain construction. In addition, the efficiency of engineered strains is still a bottleneck to scaling-up in the industry. Thus, more successful examples of highly efficient production strains need to be demonstrated by the above advanced multidisciplinary synthetic biology tools.

In this Special Issue, we ask for contributions of high-efficiency production strains driven by the latest synthetic biology tools and metabolic engineering strategies. We would like to emphasize the production of primary and secondary metabolites from engineered bacteria and yeast. These products can be biochemicals, biofuels, natural products, biomedicines, etc. We are convinced that those products will not only be important examples within the bio-economy to reach carbon neutrality but that they will also demonstrate the advancements in synthetic biology tools and metabolic engineering strategies.

Dr. Yanjun Li
Dr. Meijuan Xu
Dr. Wei Jiang
Dr. Huadong Peng
Guest Editors

Manuscript Submission Information

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Keywords

  • synthetic biology
  • metabolic engineering
  • bacteria
  • yeast
  • microbial cell factory
  • biochemicals
  • biofuel
  • natural product

Published Papers (2 papers)

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Research

15 pages, 2120 KiB  
Article
Multiple Metabolic Engineering Strategies to Improve Shikimate Titer in Escherichia coli
by Taidong Bo, Chen Wu, Zeting Wang, Hao Jiang, Feiao Wang, Ning Chen and Yanjun Li
Metabolites 2023, 13(6), 747; https://doi.org/10.3390/metabo13060747 - 12 Jun 2023
Cited by 1 | Viewed by 1398
Abstract
Shikimate is a valuable chiral precursor for synthesizing oseltamivir (Tamiflu®) and other chemicals. High production of shikimate via microbial fermentation has attracted increasing attention to overcome the unstable and expensive supply of shikimate extracted from plant resources. The current cost of [...] Read more.
Shikimate is a valuable chiral precursor for synthesizing oseltamivir (Tamiflu®) and other chemicals. High production of shikimate via microbial fermentation has attracted increasing attention to overcome the unstable and expensive supply of shikimate extracted from plant resources. The current cost of microbial production of shikimate via engineered strains is still unsatisfactory, and thus more metabolic strategies need to be investigated to further increase the production efficiency. In this study, we first constructed a shikimate E. coli producer through the application of the non-phosphoenolpyruvate: carbohydrate phosphotransferase system (non-PTS) glucose uptake pathway, the attenuation of the shikimate degradation metabolism, and the introduction of a mutant of feedback-resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase. Inspired by the natural presence of bifunctional 3-dehydroquinate dehydratase (DHD)-shikimate dehydrogenase (SDH) enzyme in plants, we then designed an artificial fusion protein of DHD-SDH to decrease the accumulation of the byproduct 3-dehydroshikimate (DHS). Subsequently, a repressed shikimate kinase (SK) mutant was selected to promote shikimate accumulation without the supplementation of expensive aromatic substances. Furthermore, EsaR-based quorum sensing (QS) circuits were employed to regulate the metabolic flux distribution between cell growth and product synthesis. The final engineered strain dSA10 produced 60.31 g/L shikimate with a yield of 0.30 g/g glucose in a 5 L bioreactor. Full article
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18 pages, 3022 KiB  
Article
Expression Silencing of Mitogen-Activated Protein Kinase 8 Interacting Protein-1 Conferred Its Role in Pancreatic β-Cell Physiology and Insulin Secretion
by Rania Saeed, Abdul Khader Mohammed, Sarra E. Saleh, Khaled M. Aboshanab, Mohammad M. Aboulwafa and Jalal Taneera
Metabolites 2023, 13(2), 307; https://doi.org/10.3390/metabo13020307 - 20 Feb 2023
Cited by 1 | Viewed by 1608
Abstract
Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) gene has been recognized as a susceptibility gene for diabetes. However, its action in the physiology of pancreatic β-cells is not fully understood. Herein, bioinformatics and genetic analyses on the publicly available database were performed to [...] Read more.
Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) gene has been recognized as a susceptibility gene for diabetes. However, its action in the physiology of pancreatic β-cells is not fully understood. Herein, bioinformatics and genetic analyses on the publicly available database were performed to map the expression of the MAPK8IP1 gene in human pancreatic islets and to explore whether this gene contains any genetic variants associated with type 2 diabetes (T2D). Moreover, a series of functional experiments were executed in a rat insulinoma cell line (INS-1 832/13) to investigate the role of the Mapk8ip1 gene in β-cell function. Metabolic engineering using RNA-sequencing (RNA-seq) data confirmed higher expression levels of MAPK8IP1 in human islets compared to other metabolic tissues. Additionally, comparable expression of MAPK8IP1 expression was detected in sorted human endocrine cells. However, β-cells exhibited higher expression of MAPK8IP1 than ductal and PSC cells. Notably, MAPK8IP1 expression was reduced in diabetic islets, and the expression was positively correlated with insulin and the β-cell transcription factor PDX1 and MAFA. Using the TIGER portal, we found that one genetic variant, “rs7115753,” in the proximity of MAPK8IP1, passes the genome-wide significance for the association with T2D. Expression silencing of Mapk8ip1 by small interfering RNA (siRNA) in INS-1 cells reduced insulin secretion, glucose uptake rate, and reactive oxygen species (ROS) production. In contrast, insulin content, cell viability, and apoptosis without cytokines were unaffected. However, silencing of Mapk8ip1 reduced cytokines-induced apoptosis and downregulated the expression of several pancreatic β-cell functional markers including, Ins1, Ins2, Pdx1, MafA, Glut2, Gck, Insr, Vamp2, Syt5, and Cacna1a at mRNA and/or protein levels. Finally, we reported that siRNA silencing of Pdx1 resulted in the downregulation of MAPK8IP1 expression in INS-1 cells. In conclusion, our findings confirmed that MAPK8IP1 is an important component of pancreatic β-cell physiology and insulin secretion. Full article
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