Biosynthesis of rhizocticins, antifungal phosphonate oligopeptides produced by Bacillus subtilis ATCC6633

Chem Biol. 2010 Jan 29;17(1):28-37. doi: 10.1016/j.chembiol.2009.11.017.

Abstract

Rhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA). Here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was heterologously produced in the nonproducer strain Bacillus subtilis 168. A biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro enzymatic conversion was characterized. Access to this intermediate allows for biochemical characterization of subsequent steps in the pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Antifungal Agents / metabolism*
  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / metabolism
  • Computational Biology
  • Molecular Sequence Data
  • Multigene Family*
  • Oligopeptides / genetics*
  • Oligopeptides / metabolism*
  • Organophosphonates / metabolism*
  • Organophosphorus Compounds / metabolism
  • Phosphotransferases (Phosphomutases) / metabolism

Substances

  • Antifungal Agents
  • Bacterial Proteins
  • Oligopeptides
  • Organophosphonates
  • Organophosphorus Compounds
  • rhizocticin B
  • Phosphotransferases (Phosphomutases)
  • phosphoenolpyruvate mutase

Associated data

  • GENBANK/FJ935779