Biosynthetic gene cluster identification and biological activity of lucilactaene from Fusarium sp. RK97-94

Biosci Biotechnol Biochem. 2020 Jun;84(6):1303-1307. doi: 10.1080/09168451.2020.1725419. Epub 2020 Feb 11.

Abstract

We identified the biosynthetic gene cluster for lucilactaene, a cell cycle inhibitor from a filamentous fungus Fusarium sp. RK 97-94. The luc1 knockout strain accumulated demethylated analogs, indicating the involvement of Luc1 methyltransferase in lucilactaene biosynthesis. Lucilactaene showed potent antimalarial activity. Our data suggested that methylation and ether ring formation are essential for its potent antimalarial activity.

Keywords: Natural products; PKS-NRPS; biological activity; biosynthesis; malaria.

MeSH terms

  • Antimalarials / metabolism*
  • Antimalarials / pharmacology
  • Cell Cycle / drug effects
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Furans / metabolism*
  • Furans / pharmacology
  • Fusarium / genetics*
  • Fusarium / metabolism*
  • Gene Knockout Techniques
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Microorganisms, Genetically-Modified
  • Multigene Family*
  • Pyrroles / metabolism*
  • Pyrroles / pharmacology

Substances

  • Antimalarials
  • Fungal Proteins
  • Furans
  • Pyrroles
  • lucilactaene
  • Methyltransferases