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

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2021 Mar 30

PMID 33784078

Citations 4

Authors

Yu-Cheng Yeh

Hak Joong Kim

Hung-Wen Liu

Affiliations

Soon will be listed here.

Abstract

AprD4 is a radical -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 . 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 elimination of the C3'-hydroxyl group rather than that of a -diol intermediate generated via 1,2-migration of the C3'-hydroxyl group to C4'. The stereochemistry of hydrogen atom incorporation after radical-mediated dehydration was also established.

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