Genetic Characterization of Neosartorin Biosynthesis Provides Insight into Heterodimeric Natural Product Generation

Org Lett. 2018 Nov 16;20(22):7197-7200. doi: 10.1021/acs.orglett.8b03123. Epub 2018 Nov 5.

Abstract

A biosynthetic gene cluster of the fungal xanthone heterodimer neosartorin (1) was discovered in Aspergillus novofumigatus, and its biosynthesis was investigated by a series of gene-deletion experiments. The results indicate that the two monomeric units of 1 are synthesized by the same set of enzymes, with chrysophanol (5) as a common precursor. Furthermore, the P450 monooxygenase NsrP for the heterodimerization was discovered, which also accepts non-native substrates to afford novel xanthone dimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Aspergillus / genetics*
  • Aspergillus / metabolism
  • Biological Products
  • Biosynthetic Pathways / genetics
  • Gene Deletion
  • Genome, Fungal
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Multigene Family*
  • Xanthones / chemical synthesis*
  • Xanthones / chemistry
  • Xanthones / metabolism
  • Xanthones / pharmacology

Substances

  • Anti-Bacterial Agents
  • Biological Products
  • Xanthones