One Polyketide Synthase, Two Distinct Products : Trans‐Acting Enzyme‐Controlled Product Divergence in Calbistrin Biosynthesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Detail(s)

Original languageEnglish
Pages (from-to)8851-8858
Journal / PublicationAngewandte Chemie - International Edition
Volume60
Issue number16
Online published22 Jan 2021
Publication statusPublished - 12 Apr 2021

Abstract

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 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.

Research Area(s)

  • biosynthesis, calbistrins, natural products, polyketide synthases, polyketides

Citation Format(s)

One Polyketide Synthase, Two Distinct Products : Trans‐Acting Enzyme‐Controlled Product Divergence in Calbistrin Biosynthesis. / Tao, Hui; Mori, Takahiro; Wei, Xingxing; Matsuda, Yudai; Abe, Ikuro.

In: Angewandte Chemie - International Edition, Vol. 60, No. 16, 12.04.2021, p. 8851-8858.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review