title: Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: cluster analysis and assignment of functions.
abstract: The biosynthetic gene cluster for the angiogenesis inhibitor borrelidin has been cloned from Streptomyces parvulus Tü4055. Sequence analysis indicates that the macrolide ring of borrelidin is formed by a modular polyketide synthase (PKS) (borA1-A6), a result that was confirmed by disruption of borA3. The borrelidin PKS is striking because only seven rather than the nine modules expected for a nonaketide product are encoded by borA1-A6. The starter unit of the PKS has been verified as trans-cyclopentane-1,2-dicarboxylic acid (trans-1,2-CPDA), and the genes involved in its biosynthesis identified. Other genes responsible for biosynthesis of the nitrile moiety, regulation, and self-resistance were also identified.
authors.affiliation: Departamento de Biologá Funcional e Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Olano
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: César
authors.initials: C
authors.lastname: Sánchez
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Moss
authors.forename: Rose
authors.initials: R
authors.lastname: Sheridan
authors.forename: Vidya
authors.initials: V
authors.lastname: Math
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Weston
authors.forename: Alfredo F
authors.initials: AF
authors.lastname: Braña
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Martin
authors.forename: Markiyan
authors.initials: M
authors.lastname: Oliynyk
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
mesh_terms: D020533:Angiogenesis Inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000138:chemical synthesis; D003998:Dicarboxylic Acids / Q000138:chemical synthesis; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism*; D005798:Genes, Bacterial; D008956:Models, Chemical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000235:genetics; D005810:Multigene Family; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D003517:Cyclopentanes; D003998:Dicarboxylic Acids; D005233:Fatty Alcohols; D009097:Multienzyme Complexes; C005066:borrelidin