Elucidating the biosynthetic pathway for the polyketide-nonribosomal peptide collismycin A: mechanism for formation of the 2,2'-bipyridyl ring

Chem Biol. 2012 Mar 23;19(3):399-413. doi: 10.1016/j.chembiol.2012.01.014.


The gene cluster for the bipyridyl compound collismycin was characterized from Streptomyces sp. CS40. Sequence analysis of a 46.7 kb DNA region revealed 27 open reading frames, 23 of which are involved in collismycin biosynthesis. Eight insertional inactivation mutants were generated in the sequenced region to prove its involvement in collismycin biosynthesis, define the boundaries of the cluster, functionally characterize some genes, and isolate two biosynthetic intermediates. A model for collismycin biosynthesis--which includes the conversion of lysine into picolinic acid, participation of a polyketide synthase-non-ribosomal peptide synthetase system, and some further modifications--is proposed. The biosynthetic pathway would include an unusual NRPS-mediated incorporation of a cysteine residue, possibly through a Michael addition and followed by the extension of the peptide chain by leucine incorporation and later removal by amidohydrolase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives*
  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / metabolism*
  • Amino Acid Sequence
  • Lysine / metabolism
  • Molecular Sequence Data
  • Multigene Family
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism*
  • Picolinic Acids / metabolism
  • Streptomyces / enzymology
  • Streptomyces / genetics


  • Picolinic Acids
  • collismycin A
  • 2,2'-Dipyridyl
  • Peptide Synthases
  • non-ribosomal peptide synthase
  • Lysine
  • picolinic acid