The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

J Antibiot (Tokyo). 2011 Jan;64(1):35-44. doi: 10.1038/ja.2010.139. Epub 2010 Nov 17.

Abstract

The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.

Publication types

  • Review

MeSH terms

  • Actinomycetales / enzymology
  • Actinomycetales / metabolism*
  • Aminobenzoates / metabolism*
  • Hydro-Lyases / metabolism*
  • Hydroxybenzoates
  • Mitomycin / biosynthesis*
  • Molecular Structure
  • Rifabutin / metabolism*

Substances

  • Aminobenzoates
  • Hydroxybenzoates
  • Rifabutin
  • Mitomycin
  • 3-amino-5-hydroxybenzoic acid
  • 3-amino-5-hydroxybenzoic acid synthase
  • Hydro-Lyases