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One Polyketide Synthase, Two Distinct Products: Trans ‐Acting Enzyme‐Controlled Product Divergence in Calbistrin Biosynthesis
Author(s) -
Tao Hui,
Mori Takahiro,
Wei Xingxing,
Matsuda Yudai,
Abe Ikuro
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202016525
Subject(s) - polyketide synthase , polyketide , biosynthesis , polyene , acyltransferase , stereochemistry , chemistry , natural product , gene cluster , enzyme , nonribosomal peptide , atp synthase , biochemistry , gene
Calbistrins are fungal polyketides consisting of the characteristic decalin and polyene moieties. Although the biosynthetic gene cluster of calbistrin A was recently identified, the pathway of calbistrin A biosynthesis has largely remained uninvestigated. Herein, we investigated the mechanism by which the backbone structures of calbistrins are formed, by heterologous and in vitro reconstitution of the biosynthesis and a structural biological study. Intriguingly, our analyses revealed that the decalin and polyene portions of calbistrins are synthesized by the single polyketide synthase (PKS) CalA, with the aid of the trans ‐acting enoylreductase CalK and the trans ‐acting C ‐methyltransferase CalH, respectively. We also determined that the esterification of the two polyketide parts is catalyzed by the acyltransferase CalD. Our study has uncovered a novel dual‐functional PKS and thus broadened our understanding of how fungi synthesize diverse polyketide natural products.