Unprecedented mechanism of chain length determination in fungal aromatic polyketide synthases

被引:36
作者
Watanabe, A [1 ]
Ebizuka, Y [1 ]
机构
[1] Univ Tokyo, Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
来源
CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 08期
基金
日本学术振兴会;
关键词
D O I
10.1016/j.chembiol.2004.05.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fungal aromatic polyketides show remarkable structural diversity fundamentally derived from variations in chain length and cyclization pattern. Their basic skeletons are synthesized by multifunctional iterative type I polyketide synthases (PKSs). Recently, we have found that the C-terminal thioesterase (TE)-like domain of Aspergillus nidulans WA catalyzes Claisen-type cyclization to form the B-ring of naphthopyrone YWA1. Here we report the unprecedented mechanism of chain length determination by the C-terminal TE-like domain of Colletotrichum lagenarium PKS1, which, in addition to catalyzing Claisen-type cyclization, intercepts the polyketomethylene intermediate from the acyl carrier protein domain during the condensation reaction to produce shorter chain length products. This chain length determination system is novel among PKSs, including bacterial and plant PKSs. The functional diversity of the TE-like domain directly influences the structural diversity of aromatic polyketides in C. lagenarium, PKS1.
引用
收藏
页码:1101 / 1106
页数:6
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