Methylations in complex carbapenem biosynthesis are catalyzed by a single cobalamin-dependent radical S-adenosylmethionine enzyme

Chem Commun (Camb). 2019 Dec 10;55(99):14934-14937. doi: 10.1039/c9cc07197k.

Abstract

Complex carbapenem β-lactam antibiotics contain diverse C6 alkyl substituents constructed by cobalamin-dependent radical SAM enzymes. TokK installs the C6 isopropyl chain found in asparenomycin. Time-course analyses of TokK and its ortholog ThnK, which forms the C6 ethyl chain of thienamycin, indicate that catalysis occurs through a sequence of discrete, non-processive methyl transfers.

MeSH terms

  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / metabolism
  • Carbapenems / biosynthesis*
  • Carbapenems / metabolism
  • Catalysis
  • Methionine Adenosyltransferase / metabolism*
  • Methylation
  • Vitamin B 12 / metabolism*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Methionine Adenosyltransferase
  • Vitamin B 12