Reassessing acetyl‐CoA supply and NADPH availability for mevalonate biosynthesis from glycerol in Escherichia coli

Mevalonate is an important platform compound for the biosynthesis of isoprenoids. It can be synthesized from acetyl‐CoA in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) by the introduced mvaES operon in Escherichia coli. The influences of E. coli hosts, acetyl‐CoA supply, and NADPH availability were assessed and engineered to improve the production titer and yield of mevalonate from glycerol. As a result, E. coli DH5α was found to be the best host with high specific capability and titer of mevalonate from glycerol. Through the engineering of phosphoketolase‐phosphotransacetylase (xPK‐PTA) bypass and NADPH availability, a final titer of 7.21 g/L with a specific capability of 1.36 g/g dry cell weight was gained in flask culture. Our work could offer new information to metabolically engineer the mevalonate pathway for the efficient production of isoprenoids. The effective acetyl‐CoA supply and nicotinamide adenine dinucleotide phosphate availability boost mevalonate biosynthesis from glycerol in Escherichia coli.