Haplofungins, novel inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 I. Taxonomy, fermentation, isolation and biological activities

J Antibiot (Tokyo). 2009 Oct;62(10):545-9. doi: 10.1038/ja.2009.72. Epub 2009 Jul 31.

Abstract

In the course of screening for antifungal agents, we have discovered eight novel compounds, haplofungin A, B, C, D, E, F, G and H, from a culture broth of the fungus strain Lauriomyces bellulus SANK 26899. Haplofungins are composed of an arabinonic acid moiety linked through an ester to a modified long alkyl chain and show potent inhibitory activities against fungal inositol phosphorylceramide (IPC) synthase. Haplofungin A inhibited the activity of IPC synthase from Saccharomyces cerevisiae with an IC(50) value of 0.0015 microg ml(-1). This inhibitor also suppressed the growth of Candida glabrata at the MIC value of 0.5 microg ml(-1).

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology*
  • Ascomycota / classification
  • Ascomycota / growth & development
  • Ascomycota / isolation & purification
  • Ascomycota / metabolism*
  • Candida glabrata / drug effects
  • Candida glabrata / enzymology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / isolation & purification
  • Fatty Acids, Unsaturated / metabolism
  • Fatty Acids, Unsaturated / pharmacology*
  • Fermentation
  • Hexosyltransferases / antagonists & inhibitors*
  • Humans
  • Microbial Sensitivity Tests
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Soil Microbiology
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Fatty Acids, Unsaturated
  • Hexosyltransferases
  • phosphatidylinositol-ceramide phosphoinositol transferase