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Publication Abstract from PubMed

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.

One Polyketide Synthase, Two Distinct Products: Trans-Acting Enzyme-Controlled Product Divergence in Calbistrin Biosynthesis.,Abe I, Tao H, Mori T, Wei X, Matsuda Y Angew Chem Int Ed Engl. 2021 Jan 22. doi: 10.1002/anie.202016525. PMID:33480463^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.