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Nat Commun. 2019 Mar 26;10(1):1378. doi: 10.1038/s41467-019-09095-z.

Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design.

Author information

1
Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 300308, Tianjin, China.
2
University of Chinese Academy of Sciences, 100049, Beijing, China.
3
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
4
School of Chemistry and Chemical Engineering, Shandong University, 250100, Jinan, Shandong, China.
5
School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
6
Center for Ecological and Environmental Sciences, Northwestern Polytechnical University, 710072, Xi'an, China.
7
School of Chemistry and Chemical Engineering, Shandong University, 250100, Jinan, Shandong, China. yongjunliu_1@sdu.edu.cn.
8
Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. yli@im.ac.cn.
9
Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 300308, Tianjin, China. jiang_hf@tib.cas.cn.

Abstract

Acetyl-CoA is a fundamental metabolite for all life on Earth, and is also a key starting point for the biosynthesis of a variety of industrial chemicals and natural products. Here we design and construct a Synthetic Acetyl-CoA (SACA) pathway by repurposing glycolaldehyde synthase and acetyl-phosphate synthase. First, we design and engineer glycolaldehyde synthase to improve catalytic activity more than 70-fold, to condense two molecules of formaldehyde into one glycolaldehyde. Second, we repurpose a phosphoketolase to convert glycolaldehyde into acetyl-phosphate. We demonstrated the feasibility of the SACA pathway in vitro, achieving a carbon yield ~50%, and confirmed the SACA pathway by 13C-labeled metabolites. Finally, the SACA pathway was verified by cell growth using glycolaldehyde, formaldehyde and methanol as supplemental carbon source. The SACA pathway is proved to be the shortest, ATP-independent, carbon-conserving and oxygen-insensitive pathway for acetyl-CoA biosynthesis, opening possibilities for producing acetyl-CoA-derived chemicals from one-carbon resources in the future.

PMID:
30914637
PMCID:
PMC6435721
DOI:
10.1038/s41467-019-09095-z
[Indexed for MEDLINE]
Free PMC Article

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