Elucidation of key enzymes involved in the formation of atypical polyketide extender unit

November 12, 2015

The first step in structural diversification of bioactive natural compounds

RIKEN CSRS researchers have shed light on the biosynthesis of unique extender units (2-alkylmalonyl-CoA) for the formation of polyketide compounds. Polyketides compounds are naturally produced by microorganisms. A particularly well-known example is the four distinct analogues of reveromycin produced by Streptomyces sp. SN-593. Reveromycin derivatives contain the atypical polyketide extender unit. To investigate the function of genes related to the biosynthesis of 2-alkylmalonyl-CoA, we constructed gene disruption and analyzed their metabolite profiles. Moreover, we biochemically characterized the enzyme functions to reveal the biosynthetic mechanism of 2-alkylmalonyl-CoA. The understanding of atypical 2-alkylmalonyl-CoA biosynthesis is expected to contribute to expanded structural diversity of polyketide compound for a drug seed.

Original article

The Journal of Biological Chemistry doi: 10.1074/jbc.M115.677195

T. Miyazawa, S. Takahashi, A. Kawata, S. Panthee, T. Hayashi, T. Shimizu, T. Nogawa, H. Osada,

"Identification of middle chain fatty acyl-CoA ligase responsible for the biosynthesis of 2-alkylmalonyl-CoAs for polyketide extender unit".

Contact

Shunji Takahashi

Unit Leader

Natural Product Biosynthesis Research Unit