Enzymatic Reconstitution and Biosynthetic Investigation of the Bacterial Carbazole Neocarazostatin A

J Org Chem. 2019 Dec 20;84(24):16323-16328. doi: 10.1021/acs.joc.9b02688. Epub 2019 Nov 26.

Abstract

Tricyclic carbazole is an important scaffold in many naturally occurring metabolites, as well as valuable building blocks. Here we report the reconstitution of the ring A formation of the bacterial neocarazostatin A carbazole metabolite. We provide evidence of the involvement of two unusual aromatic polyketide proteins. This finding suggests how new enzymatic activities can be recruited to specific pathways to expand biosynthetic capacities. Finally, we leveraged our bioinformatics survey to identify the untapped capacity of carbazole biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbazoles / chemistry
  • Carbazoles / isolation & purification
  • Carbazoles / metabolism*
  • Computational Biology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Molecular Structure
  • Streptomyces / chemistry*
  • Transferases / metabolism*

Substances

  • Carbazoles
  • neocarazostatin A
  • Cytochrome P-450 Enzyme System
  • Transferases