title: Generation by mutasynthesis of potential neuroprotectant derivatives of the bipyridyl collismycin A.
abstract: 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.
authors.affiliation: Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A.), Universidad de Oviedo, Oviedo 33006, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sialer
authors.forename: Ignacio
authors.initials: I
authors.lastname: García
authors.forename: Javier
authors.initials: J
authors.lastname: González-Sabín
authors.forename: Alfredo F
authors.initials: AF
authors.lastname: Braña
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
authors.forename: Francisco
authors.initials: F
authors.lastname: Morís
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D007814:Larva / Q000187:drug effects; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010848:Picolinic Acids / Q000494:pharmacology; D013302:Streptomyces / Q000201:enzymology; D000637:Transaminases / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development
chemical_list: D018696:Neuroprotective Agents; D010848:Picolinic Acids; C089907:collismycin A; D015082:2,2'-Dipyridyl; D000637:Transaminases; C113111:lysine 2-aminotransferase; C030614:picolinic acid
keywords: Nonribosomal peptide; Polyketide; Streptomyces