Short branched-chain acyl-CoAs are important building blocks for a wide variety of pharmaceutically valuable natural products, such as avermectins, lovastatins, antimycin A, bitter acids and α-lipomycin. Native E. coli metabolism, however, does not produce these short branched-chain acyl-CoAs, which hampers the heterologous production of many valuable compounds in this host.

In the current study, researchers from Tianjin Institute of Industrial Biotechnology, CAS, engineered synthesis of isobutyryl-CoA and isovaleryl-CoA from glucose in E. coli by integration of the branched-chain α-keto acid dehydrogenase complex from Streptomyces avermitilis. Furthermore, they enhanced the synthesis of isobutyryl-CoA and isovaleryl-CoA by improving the α-keto acid precursor supply. This report of synthesis of short branched-chain acyl-CoAs in E. coli opens a way to biosynthesize various valuable natural compounds based on these special building blocks in E. coli from renewable carbon sources.

Entitled “Engineered short branched-chain acyl-CoA synthesis in E. coli and acylation of chloramphenicol

to branched-chain derivatives” , this research was published online in Appl Microbiol Biotechnol on October 08, 2013. This work was supported by National Program on Key Basic Research Project of China (973 Program) and National High-tech R&D Program of China (863 Program). (Provided by Prof. Tao Liu’s group)