Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain

被引：13

作者：

Hang, Leibniz ^{[1
]}

Tang, Man-Cheng ^{[1
]}

Harvey, Colin J. B. ^{[2
]}

Page, Claire G. ^{[1
]}

Li, Jian ^{[2
]}

Hung, Yiu-Sun ^{[1
]}

Liu, Nicholas ^{[1
]}

Hillenmeyer, Maureen E. ^{[2
]}

Tang, Yi ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[2] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 93404 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2017年 / 56卷 / 32期

关键词：

acyltransferase; biosynthesis; heterologous expression; methyltransferase; polyketides; BIOSYNTHETIC GENE-CLUSTER; CRYSTAL-STRUCTURES; ESCHERICHIA-COLI; ACETYLTRANSFERASE; SYNTHETASE; YERSINIABACTIN; ENZYMOLOGY; TRANSPORT; SYMBIONT; REVEALS;

D O I：

10.1002/anie.201705237

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 alpha-methylation steps on the last beta-keto intermediate to yield an alpha,alpha-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.

引用

页码：9556 / 9560

页数：5

共 24 条

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