Discovery of a Diazo-Forming Enzyme in Cremeomycin Biosynthesis

J Org Chem. 2018 Jul 20;83(14):7539-7546. doi: 10.1021/acs.joc.8b00367. Epub 2018 May 29.


The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show that the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology as well as enable genome-based discovery of new diazo-containing metabolites.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azo Compounds / chemistry
  • Azo Compounds / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biocatalysis
  • Cyclohexanones / chemistry
  • Cyclohexanones / metabolism
  • Gene Expression Regulation, Bacterial / physiology*
  • Gene Expression Regulation, Enzymologic / physiology*
  • Molecular Structure
  • Protein Biosynthesis / physiology*
  • Streptomyces / enzymology*
  • Streptomyces / metabolism


  • Azo Compounds
  • Bacterial Proteins
  • Cyclohexanones
  • cremeomycin