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

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. Enzyme-mediated oxidative cyclizations in nature are a powerful demonstration of the utility of selective C–H activation. Here, Rieske oxygenase-like enzymes RedG and McpG are shown to mediate regio- and stereodivergent carbocyclization of undecylprodigiosin to streptorubin B and metacycloprodigiosin, respectively. Understanding these remarkably selective C–H activations could inspire the design of biomimetic catalysts with similar capabilities.

Cite this article

Sydor, P., Barry, S., Odulate, O. et al. Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes. Nature Chem 3, 388–392 (2011). https://doi.org/10.1038/nchem.1024

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