Short pathways to complexity generation: fungal peptidyl alkaloid multicyclic scaffolds from anthranilate building blocks

ACS Chem Biol. 2013 Jul 19;8(7):1366-82. doi: 10.1021/cb4001684. Epub 2013 Jun 4.

Abstract

Complexity generation in naturally occurring peptide scaffolds can occur either by posttranslational modifications of nascent ribosomal proteins or through post assembly line tailoring of nonribosomal peptides. Short enzymatic pathways utilizing bimodular and trimodular nonribosomal peptide synthetase (NRPS) assembly lines, followed by tailoring oxygenases and/or prenyltransferases, efficiently construct complex fungal peptidyl alkaloid scaffolds in Aspergilli, Neosartorya, and Penicillium species. Use of the nonproteinogenic amino acid anthranilate as chain-initiating building block and chain-terminating intramolecular nucleophile leads efficiently to peptidyl alkaloid scaffolds with two to seven fused rings.

Publication types

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

MeSH terms

  • Alkaloids / chemistry*
  • Fungi / chemistry*
  • Gliotoxin / chemistry
  • Indoles / chemistry
  • Molecular Structure
  • Peptide Synthases / chemistry
  • Peptides / chemistry*
  • Piperazines / chemistry
  • Spiro Compounds / chemistry
  • ortho-Aminobenzoates / chemistry*

Substances

  • Alkaloids
  • Indoles
  • Peptides
  • Piperazines
  • Spiro Compounds
  • ortho-Aminobenzoates
  • anthranilic acid
  • brevianamide A
  • Gliotoxin
  • tryptoquivaline
  • Peptide Synthases
  • non-ribosomal peptide synthase