NDLI: Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum

Content Provider	Springer Nature : BioMed Central
Author	Lu, Lingxue Mao, Yufeng Kou, Mengyun Cui, Zhenzhen Jin, Biao Chang, Zhishuai Wang, Zhiwen Ma, Hongwu Chen, Tao
Abstract	Background Acetoin, especially the optically pure (3S)- or (3R)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the production of optically pure acetoin enantiomers are rarely reported. Previously, we systematically engineered the GRAS microorganism Corynebacterium glutamicum to efficiently produce (3R)-acetoin from glucose. Nevertheless, its yield and average productivity were still unsatisfactory for industrial bioprocesses. Results In this study, cellular carbon fluxes in the acetoin producer CGR6 were further redirected toward acetoin synthesis using several metabolic engineering strategies, including blocking anaplerotic pathways, attenuating key genes of the TCA cycle and integrating additional copies of the alsSD operon into the genome. Among them, the combination of attenuation of citrate synthase and inactivation of phosphoenolpyruvate carboxylase showed a significant synergistic effect on acetoin production. Finally, the optimal engineered strain CGS11 produced a titer of 102.45 g/L acetoin with a yield of 0.419 g/g glucose at a rate of 1.86 g/L/h in a 5 L fermenter. The optical purity of the resulting (3R)-acetoin surpassed 95%. Conclusion To the best of our knowledge, this is the highest titer of highly enantiomerically enriched (3R)-acetoin, together with a competitive product yield and productivity, achieved in a simple, green processes without expensive additives or substrates. This process therefore opens the possibility to achieve easy, efficient, economical and environmentally-friendly production of (3R)-acetoin via microbial fermentation in the near future.
Related Links	https://microbialcellfactories.biomedcentral.com/counter/pdf/10.1186/s12934-020-01363-8.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	14752859
DOI	10.1186/s12934-020-01363-8
Journal	Microbial Cell Factories
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2020-05-12
Access Restriction	Open
Subject Keyword	Applied Microbiology Biotechnology Microbiology Microbial Genetics and Genomics Enzymology Genetic Engineering Corynebacterium glutamicum (3R)-Acetoin Metabolic engineering Microbial fermentation Citrate synthase Green chemistry
Content Type	Text
Resource Type	Article
Subject	Applied Microbiology and Biotechnology Bioengineering Biotechnology
Journal Impact Factor	4.3/2023
5-Year Journal Impact Factor	5.5/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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