title: Expanding Radical SAM Chemistry by Using Radical Addition Reactions and SAM Analogues.
abstract: Radical S-adenosyl-l-methionine (SAM) enzymes utilize a [4Fe-4S] cluster to bind SAM and reductively cleave its carbon-sulfur bond to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical. In almost all cases, the dAdo radical abstracts a hydrogen atom from the substrates or from enzymes, thereby initiating a highly diverse array of reactions. Herein, we report a change of the dAdo radical-based chemistry from hydrogen abstraction to radical addition in the reaction of the radical SAM enzyme NosL. This change was achieved by using a substrate analogue containing an olefin moiety. We also showed that two SAM analogues containing different nucleoside functionalities initiate the radical-based reactions with high efficiencies. The radical adduct with the olefin produced in the reaction was found to undergo two divergent reactions, and the mechanistic insights into this process were investigated in detail. Our study demonstrates a promising strategy in expanding radical SAM chemistry, providing an effective way to access nucleoside-containing compounds by using radical SAM-dependent reactions.
authors: Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.|Department of Chemistry, Fudan University, Shanghai, 200433, China.
authors: Xinjian
authors: X
authors: Ji
authors: Department of Chemistry, Fudan University, Shanghai, 200433, China.
authors: Yongzhen
authors: Y
authors: Li
authors: Department of Chemistry, Fudan University, Shanghai, 200433, China.
authors: Liqi
authors: L
authors: Xie
authors: Department of Chemistry, Fudan University, Shanghai, 200433, China.
authors: Haojie
authors: H
authors: Lu
authors: Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China. dingw@lzu.edu.cn.
authors: Wei
authors: W
authors: Ding
authors: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors: Qi
authors: 0000-0002-8135-2221
authors: Q
authors: Zhang
keywords: S-adenosylmethionine; SAM analogues; biosynthesis; radical addition; thiopeptides