Generation of novel landomycins M and O through targeted gene disruption

Chembiochem. 2005 Apr;6(4):675-8. doi: 10.1002/cbic.200400316.

Abstract

Two genes from Streptomyces cyanogenous S136 that encode the reductase LanZ4 and the hydroxylase LanZ5, which are involved in landomycin A biosynthesis, were characterized by targeted gene inactivation. Analyses of the corresponding mutants as well as complementation experiments have allowed us to show that LanZ4 and LanZ5 are responsible for the unique C-11-hydroxylation that occurs during landomycin biosynthesis. Compounds accumulated by the lanZ4/Z5 mutants are the previously described landomycin F and the new landomycins M and O.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / biosynthesis*
  • Aminoglycosides / pharmacology
  • Antibiotics, Antineoplastic / biosynthesis
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disaccharides / biosynthesis*
  • Disaccharides / pharmacology
  • Gene Targeting*
  • Humans
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology
  • Oligosaccharides / biosynthesis*
  • Oligosaccharides / chemistry
  • Oligosaccharides / pharmacology
  • Oxygenases / genetics
  • Streptomyces / genetics*
  • Streptomyces / metabolism

Substances

  • Aminoglycosides
  • Antibiotics, Antineoplastic
  • Disaccharides
  • Naphthoquinones
  • Oligosaccharides
  • landomycin M
  • landomycin O
  • landomycinone
  • Oxygenases