we design the non-carboxylative malonyl-coa pathway as a non-natural route for malonyl-coa biosynthesis, independent from acetyl-coa. the designed pathway features enzymes such as β-alanine-pyruvate transaminase and malonyl-coa reductase, exhibits fast kinetics and circumvents tight regulations and the architecture associated with the natural pathway. furthermore, introducing this pathway into microbes enhances the production of mdps, including short-chain fatty acids and representative phenol, quinone, alkene, aminoglycoside and macrolide polyketide families, such as spinosad. in summary, this malonyl-coa formation pathway avoids intrinsic inefficiencies of the natural pathway and can serve as a versatile platform for obtaining mdps that could be used as fuels, fine chemicals and pharmaceuticals.
