Generation by mutasynthesis of potential neuroprotectant derivatives of the bipyridyl collismycin A

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5707-9. doi: 10.1016/j.bmcl.2013.08.017. Epub 2013 Aug 12.


Collismycin A is a member of the 2,2'-bipyridyl family of natural products and structurally belongs to the hybrid polyketides-nonribosomal peptides. A gene coding for a lysine 2-aminotransferase of Streptomyces sp. CS40 (collismycin A producer) was inactivated by gene replacement. The mutant was unable of synthesizing collismycin A but it recovered this capability when picolinic acid was added to the culture medium. By feeding different picolinic acid analogs to this mutant, two new collismycin A derivatives were obtained with a methyl group at the 4 and 6 position of the first pyridine ring of collismycin A, respectively. The two compounds showed effective neuroprotective action against an oxidative stress inducer in a zebra fish model, one of them showing higher neuroprotectant activity than that of collismycin A and that of the control lipoic acid.

Keywords: Nonribosomal peptide; Polyketide; Streptomyces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives*
  • 2,2'-Dipyridyl / chemical synthesis
  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / pharmacology
  • Animals
  • Larva / drug effects
  • Models, Animal
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Picolinic Acids / pharmacology
  • Streptomyces / enzymology
  • Transaminases / genetics
  • Transaminases / metabolism
  • Zebrafish / growth & development


  • Neuroprotective Agents
  • Picolinic Acids
  • collismycin A
  • 2,2'-Dipyridyl
  • Transaminases
  • lysine 2-aminotransferase
  • picolinic acid