Biosynthesis of the tunicamycins: a review

J Antibiot (Tokyo). 2007 Aug;60(8):485-91. doi: 10.1038/ja.2007.62.

Abstract

Tunicamycins are nucleotide sugar analogs produced by several Streptomyces species. In eukaryotes, tunicamycins inhibit UDP-N-acetylglucosamine: dolichol phosphate GlcNAc-1-P transferase (GPT) that catalyzes the first step in protein glycosylation. In bacteria they inhibit UDP-N-acetylmuramoyl-pentapeptide: undecaprenol phosphate MurNAc-pentapeptide-1-P transtransferase (MraY) that catalyzes an early stage in peptidoglycan cell wall assembly. Tunicamycins are substrate analog of GPT and MraY, such that the alphabeta-1'',11'-linked GlcNAc residue of the tunicamycins mimics the transferred GlcNAc-1-phosphate. The unusual structure of tunicamycins, particularly the unique 11-carbon sugar, tunicamine, and the alphabeta-1'',11'-O-glycosidic linkage, suggest its biosynthesis to be unique. This review discusses potential biosyntheses for tunicamycins via the synthesis and conjugation of uridine-5'-aldehyde and UDP-4-keto-N-acetylgalactosamine-5,6-ene and the subsequent formation of the alpha,beta-1'',11' glycosidic linkage.

Publication types

  • Review

MeSH terms

  • Aldehydes / metabolism
  • Carbohydrate Conformation
  • Disaccharides
  • Galactosamine / analogs & derivatives
  • Glycosides / metabolism
  • Glycosylation
  • Oxidoreductases / metabolism
  • Phosphorus-Oxygen Lyases / metabolism
  • Proteins / metabolism
  • Streptomyces / metabolism
  • Tunicamycin / biosynthesis*
  • Tunicamycin / chemistry
  • Uridine / metabolism

Substances

  • Aldehydes
  • Disaccharides
  • Glycosides
  • Proteins
  • Tunicamycin
  • tunicamine
  • Galactosamine
  • Oxidoreductases
  • 3-dehydroquinate synthetase
  • Phosphorus-Oxygen Lyases
  • Uridine