生物合成
部分
化学
基质(水族馆)
立体化学
酶
生物化学
组合化学
生物
生态学
作者
Hong Zhu,Bo Zhang,Wanqing Wei,Shuang He Liu,Lang Xiang,Jiapeng Zhu,Rui Jiao,Yasuhiro Igarashi,Ghader Bashiri,Yong Liang,Ren Xiang Tan,Hui Ge
标识
DOI:10.1038/s41467-022-32088-4
摘要
Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1). We show through in vivo gene deletion, in vitro biochemical assay and isotope labelling experiments that AvmM catalyzes tandem dehydration and Michael-type addition to generate the core scaffold of 1. Mechanistic studies by crystallography, DFT calculations and MD simulations of AvmM reveal that the reactions are achieved with assistance from the special tenuazonic acid like moiety of substrate. Our results thus uncover an uncharacterized macrocyclization strategy in natural product biosynthesis.
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