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

Yu Cheng Yeh, Hak Joong Kim, Hung Wen Liu

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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 elimination of the C3′-hydroxyl group rather than that of a gem-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.

Original languageEnglish
Pages (from-to)5038-5043
Number of pages6
JournalJournal of the American Chemical Society
Volume143
Issue number13
DOIs
Publication statusPublished - 2021 Apr 7
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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