The dynamic structure of jadomycin B and the amino acid incorporation step of its biosynthesis

J Am Chem Soc. 2004 Apr 14;126(14):4496-7. doi: 10.1021/ja031724o.

Abstract

Jadomycin B, an antifungal antibiotic with a unique 8H-benz[b]oxazolo[3,2-f]phenanthridine pentacyclic skeleton produced by the bacterium Streptomyces venezuelae ISP 5230, exists in a dynamic equilibrium of two diastereomers differing in the configuration of C-3a. Several novel jadomycins with various amino acid-derived 1-side chains could be generated, by replacing isoleucine in the production medium of S. venezuelae with other amino acids. These two findings led to the conclusion that a nonenzymatic reaction with the amino acid followed by a likewise nonenzymatic cyclization cascade are crucial for its late biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism*
  • Hydrogen Bonding
  • Isoleucine / chemistry
  • Isoleucine / metabolism
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism*
  • Models, Molecular
  • Molecular Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Stereoisomerism

Substances

  • Amino Acids
  • Isoquinolines
  • Isoleucine
  • jadomycin B