Biochemical Characterization of NotB as an FAD-Dependent Oxidase in the Biosynthesis of Notoamide Indole Alkaloids

作者：Shengying Li, Jennifer M. Finefield, James D. Sunderhaus, Timothy J. McAfoos, Robert M. Williams, David H. Sherman · 发表于：Journal of the American Chemical Society · 年份：2011 · DOI：10.1021/ja2093212 · 被引用次数：132 · 研究领域：Microbial Natural Products and Biosynthesis、Alkaloids: synthesis and pharmacology、Microbial Metabolism and Applications

Notoamides produced by Aspergillus spp. bearing the bicyclo[2.2.2]diazaoctane core structure with unusual structural diversity represent a compelling system to understand the biosynthesis of fungal prenylated indole alkaloids. Herein, we report the in vitro characterization of NotB, which catalyzes the indole 2,3-oxidation of notoamide E (13), leading to notoamides C (11) and D (12) through an apparent pinacol-like rearrangement. This unique enzymatic reaction with high substrate specificity, together with the information derived from precursor incorporation experiments using [(13)C](2)-[(15)N](2) quadruply labeled notoamide S (10), demonstrates 10 as a pivotal branching point in notoamide biosynthesis.