title: Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes.
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.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Paulina K
authors.initials: PK
authors.lastname: Sydor
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Barry
authors.forename: Olanipekun M
authors.initials: OM
authors.lastname: Odulate
authors.forename: Francisco
authors.initials: F
authors.lastname: Barona-Gomez
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Haynes
authors.forename: Christophe
authors.initials: C
authors.lastname: Corre
authors.forename: Lijiang
authors.initials: L
authors.lastname: Song
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Challis
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D055162:Biocatalysis; D003500:Cyclization; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D010105:Oxygenases