The Cremeomycin Biosynthetic Gene Cluster Encodes a Pathway for Diazo Formation

Chembiochem. 2015 Oct 12;16(15):2172-5. doi: 10.1002/cbic.201500407. Epub 2015 Sep 14.


Diazo groups are found in a range of natural products that possess potent biological activities. Despite longstanding interest in these metabolites, diazo group biosynthesis is not well understood, in part because of difficulties in identifying specific genes linked to diazo formation. Here we describe the discovery of the gene cluster that produces the o-diazoquinone natural product cremeomycin and its heterologous expression in Streptomyces lividans. We used stable isotope feeding experiments and in vitro characterization of biosynthetic enzymes to decipher the order of events in this pathway and establish that diazo construction involves late-stage N-N bond formation. This work represents the first successful production of a diazo-containing metabolite in a heterologous host, experimentally linking a set of genes with diazo formation.

Keywords: biosynthesis; diazo compounds; enzymes; heterologous expression; natural products.

Publication types

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

MeSH terms

  • Azo Compounds / chemistry
  • Azo Compounds / metabolism*
  • Biosynthetic Pathways / genetics*
  • Cyclohexanones / chemistry
  • Cyclohexanones / metabolism
  • Molecular Structure
  • Multigene Family*
  • Streptomyces lividans / chemistry
  • Streptomyces lividans / metabolism


  • Azo Compounds
  • Cyclohexanones
  • cremeomycin