Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes

Paulina K. Sydor, Sarah M. Barry, Olanipekun M. Odulate, Francisco Barona-Gomez, Stuart W. Haynes, Christophe Corre, Lijiang Song, Gregory L. Challis

Research output: Contribution to journalArticleResearchpeer-review

74 Citations (Scopus)

Abstract

Oxidative cyclizations, exemplified by the biosynthetic assembly of the penicillin nucleus from a tripeptide precursor, are arguably the most synthetically powerful implementation of C-H activation reactions in nature. Here, we show that Rieske oxygenase-like enzymes mediate regio- and stereodivergent oxidative cyclizations to form 10- and 12-membered carbocyclic rings in the key steps of the biosynthesis of the antibiotics streptorubin B and metacycloprodigiosin, respectively. These reactions represent the first examples of oxidative carbocyclizations catalysed by non-haem iron-dependent oxidases and define a novel type of catalytic activity for Rieske enzymes. A better understanding of how these enzymes achieve such remarkable regio- and stereocontrol in the functionalization of unactivated hydrocarbon chains will greatly facilitate the development of selective man-made C-H activation catalysts.

Original languageEnglish
Pages (from-to)388-392
Number of pages5
JournalNature Chemistry
Volume3
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

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