Identification of a Biosynthetic Gene Cluster Responsible for the Production of a New Pyrrolopyrimidine Natural Product-Huimycin

Biomolecules. 2020 Jul 18;10(7):1074. doi: 10.3390/biom10071074.

Abstract

Pyrrolopyrimidines are an important class of natural products with a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, anticancer or anti-inflammatory. Here, we present the identification of a biosynthetic gene cluster from the rare actinomycete strain Kutzneria albida DSM 43870, which leads to the production of huimycin, a new member of the pyrrolopyrimidine family of compounds. The huimycin gene cluster was successfully expressed in the heterologous host strain Streptomyces albus Del14. The compound was purified, and its structure was elucidated by means of nuclear magnetic resonance spectroscopy. The minimal huimycin gene cluster was identified through sequence analysis and a series of gene deletion experiments. A model for huimycin biosynthesis is also proposed in this paper.

Keywords: heterologous expression; kutzneria; nucleoside; pyrrolopyrimidines; secondary metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / genetics*
  • Actinobacteria / metabolism
  • Biological Products / metabolism*
  • Biosynthetic Pathways*
  • Gene Expression
  • Genes, Bacterial
  • Multigene Family*
  • Pyrimidines / metabolism*
  • Pyrroles / metabolism*
  • Streptomyces / genetics
  • Streptomyces / metabolism

Substances

  • Biological Products
  • Pyrimidines
  • Pyrroles
  • pyrrolopyrimidine

Supplementary concepts

  • Kutzneria albida
  • Streptomyces albus