2. Academic Validation
  3. The Cremeomycin Biosynthetic Gene Cluster Encodes a Pathway for Diazo Formation

The Cremeomycin Biosynthetic Gene Cluster Encodes a Pathway for Diazo Formation

  • Chembiochem. 2015 Oct 12;16(15):2172-5. doi: 10.1002/cbic.201500407.
Abraham J Waldman 1,  Yakov Pechersky 1,  Peng Wang 1,  Jennifer X Wang 2,  Emily P Balskus 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA.
  • 2 Small Molecule Mass Spectrometry Facility, Faculty of Arts and Sciences Division of Science, Harvard University, 52 Oxford Street, Cambridge, MA, 02138, USA.
  • 3 Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA. balskus@chemistry.harvard.edu.
PMID: 26278892 DOI: 10.1002/cbic.201500407
Abstract

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.

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