title: Elucidating the biosynthetic pathway for the polyketide-nonribosomal peptide collismycin A: mechanism for formation of the 2,2'-bipyridyl ring.
abstract: 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.
authors.affiliation: Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias-I.U.O.P.A, Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garcia
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Vior
authors.forename: Alfredo F
authors.initials: AF
authors.lastname: Braña
authors.forename: Javier
authors.initials: J
authors.lastname: González-Sabin
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rohr
authors.forename: Francisco
authors.initials: F
authors.lastname: Moris
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D010848:Picolinic Acids / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics
chemical_list: D010848:Picolinic Acids; C089907:collismycin A; D015082:2,2'-Dipyridyl; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase; D008239:Lysine; C030614:picolinic acid