Disciformycins A and B: 12-membered macrolide glycoside antibiotics from the myxobacterium Pyxidicoccus fallax active against multiresistant staphylococci

Angew Chem Int Ed Engl. 2014 Dec 1;53(49):13588-91. doi: 10.1002/anie.201406973. Epub 2014 Oct 7.

Abstract

Two macrolide glycosides with a unique scaffold were isolated from cultures of the myxobacterium Pyxidicoccus fallax. Their structures, including absolute configurations, were elucidated by a combination of NMR, MS, degradation, and molecular modeling techniques. Analysis of the proposed biosynthetic gene cluster led to insights into the biosynthesis of the polyketide and confirmed the structure assignment. The more active compound, disciformycin B, potently inhibits methicillin- and vancomycin-resistant Staphylococcus aureus.

Keywords: antibiotics; biosynthesis; myxobacteria; polyketides; secondary metabolites.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Humans
  • Macrolides / chemistry*
  • Macrolides / isolation & purification
  • Macrolides / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Myxococcales / chemistry*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Vancomycin Resistance

Substances

  • Anti-Bacterial Agents
  • Macrolides