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Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain
Author(s) -
Hang Leibniz,
Tang ManCheng,
Harvey Colin J. B.,
Page Claire G.,
Li Jian,
Hung YiuSun,
Liu Nicholas,
Hillenmeyer Maureen E.,
Tang Yi
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201705237
Subject(s) - polyketide synthase , acyltransferase , polyketide , natural product , chemistry , biochemistry , biosynthesis , stereochemistry , nucleophile , biology , enzyme , catalysis
Abstract Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C‐terminal domain with significant homology to carnitine O ‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. This process is readily reversible, as confirmed through the holo ACP‐dependent transesterification of the released product. The methyltransferase (MT) domain of Tv6‐931 can perform two consecutive α‐methylation steps on the last β‐keto intermediate to yield an α,α‐ gem ‐dimethyl product, a new programing feature among HRPKSs. Recapturing of the released product by cAT domain is suggested to facilitate complete gem ‐dimethylation by the MT.