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Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum.
Microb Cell Fact. 2020 May 12; 19(1):102.MC

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.

Authors+Show Affiliations

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China. chentao@tju.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32398078

Citation

Lu, Lingxue, et al. "Engineering Central Pathways for Industrial-level (3R)-acetoin Biosynthesis in Corynebacterium Glutamicum." Microbial Cell Factories, vol. 19, no. 1, 2020, p. 102.
Lu L, Mao Y, Kou M, et al. Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum. Microb Cell Fact. 2020;19(1):102.
Lu, L., Mao, Y., Kou, M., Cui, Z., Jin, B., Chang, Z., Wang, Z., Ma, H., & Chen, T. (2020). Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum. Microbial Cell Factories, 19(1), 102. https://doi.org/10.1186/s12934-020-01363-8
Lu L, et al. Engineering Central Pathways for Industrial-level (3R)-acetoin Biosynthesis in Corynebacterium Glutamicum. Microb Cell Fact. 2020 May 12;19(1):102. PubMed PMID: 32398078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum. AU - Lu,Lingxue, AU - Mao,Yufeng, AU - Kou,Mengyun, AU - Cui,Zhenzhen, AU - Jin,Biao, AU - Chang,Zhishuai, AU - Wang,Zhiwen, AU - Ma,Hongwu, AU - Chen,Tao, Y1 - 2020/05/12/ PY - 2020/02/23/received PY - 2020/05/05/accepted PY - 2020/5/14/entrez PY - 2020/5/14/pubmed PY - 2020/5/14/medline KW - (3R)-Acetoin KW - Citrate synthase KW - Corynebacterium glutamicum KW - Green chemistry KW - Metabolic engineering KW - Microbial fermentation SP - 102 EP - 102 JF - Microbial cell factories JO - Microb. Cell Fact. VL - 19 IS - 1 N2 - 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. SN - 1475-2859 UR - https://www.unboundmedicine.com/medline/citation/32398078/Engineering_central_pathways_for_industrial-level_(3R)-acetoin_biosynthesis_in_Corynebacterium_glutamicum L2 - https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-020-01363-8 DB - PRIME DP - Unbound Medicine ER -
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