Mechanistic Investigation of 1,2-Diol Dehydration of Paromamine Catalyzed by the Radical S-Adenosyl-l-methionine Enzyme AprD4.

ABSTRACT: AprD4 is a radical S-adenosyl-l-methionine (SAM) enzyme catalyzing C3'-deoxygenation of paromamine to form 4'-oxo-lividamine. It is the only 1,2-diol dehydratase in the radical SAM enzyme superfamily that has been identified and characterized in vitro. The AprD4 catalyzed 1,2-diol dehydration is a key step in the biosynthesis of several C3'-deoxy-aminoglycosides. While the regiochemistry of the hydrogen atom abstraction catalyzed by AprD4 has been established, the mechanism of the subsequent chemical transformation remains not fully understood. To investigate the mechanism, several substrate analogues were synthesized and their fates upon incubation with AprD4 were analyzed. The results support a mechanism involving formation of a ketyl radical intermediate followed by direct

SUBMITTER: Yeh YC 

PROVIDER: S-EPMC8045149 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature