Iterative Catalysis in the Biosynthesis of Mitochondrial Complex II Inhibitors Harzianopyridone and Atpenin B

被引：32

作者：

Bat-Erdene, Undramaa ^{[1
]}

Kanayama, Daiki ^{[2
]}

Tan, Dan ^{[1
]}

Turner, William C. ^{[1
]}

Houk, K. N. ^{[1
,2
]}

Ohashi, Masao ^{[1
]}

Tang, Yi ^{[1
,2
]}

机构：

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

[2] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2020年 / 142卷 / 19期

关键词：

2-PYRIDONE TENELLIN; POTENT;

D O I：

10.1021/jacs.0c03438

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The pentasubstituted pyridine natural products harzianopyridone and atpenins are potent inhibitors of mitochondrial complex II. We identified the pathways of these compounds from their fungal producers and uncovered that the biosynthetic steps require multiple iterative enzymes. In particular, a methyltransferase and a flavin-dependent monooxygenase are used iteratively to introduce C5 and C6 methoxy groups. The pathway unexpectedly requires the installation and removal of an N-methoxy group, which is proposed to be a directing group that tunes the reactivity of the pyridone ring, possibly through the alpha effect.

引用

页码：8550 / 8554

页数：5

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