Discovery of a new carboxylase

Novel biosynthetic pathway creates structural diversity in natural organic compounds

An international collaborative research group from RIKEN CSRS, the University of California, Irvine and the University of Warwick have elucidated a novel biosynthetic pathway that creates structural diversity in natural organic compounds.

Analyzing the biosynthetic mechanisms of polyketide compounds in the antibiotics stambomycin and reveromycin, researchers speculated alkylmalonyl-CoA pathways that did not use crotonyl-CoA reductase/carboxylase (CCR). They found a novel polyketide biosynthetic pathway involving the SamR0483 enzyme, which carboxylates acyl-CoA intermediates. Using bioengineering methods, researchers were able to successfully create new stambomycin analogues that can serve as tags useful for intracellular tracking of drugs with alkynes and azide groups, and for identifying target proteins.

The biosynthetic system elucidated in this research should contribute not only to the diversity of structural compounds, but should also be useful as a tool for introducing tags that will help shed light on the mechanisms of action for natural organic compounds.


Original article
Nature Communications doi:10.1038/NCOMMS13609
L. Ray, T. Valentic, T. Miyazawa, D. M. Withall, L. Song, J. C. Milligan, H. Osada, S. Takahashi, S. Tsai, G. L. Challis,
"A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units".

Shunji Takahashi
Unit Leasder
Natural Product Biosynthesis Research Unit