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

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 glycola

SUBMITTER: Lu X 

PROVIDER: S-EPMC6435721 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature