title: Characterization of the biosynthetic gene cluster for the antifungal polyketide soraphen A from Sorangium cellulosum So ce26.
abstract: A genomic DNA region of over 80 kb that contains the complete biosynthetic gene cluster for the synthesis of the antifungal polyketide metabolite soraphen A was cloned from Sorangium cellulosum So ce26. The nucleotide sequence of the soraphen A gene region, including 67,523 bp was determined. Examination of this sequence led to the identification of two adjacent type I polyketide synthase (PKS) genes that encode the soraphen synthase. One of the soraphen A PKS genes includes three biosynthetic modules and the second contains five additional modules for a total of eight. The predicted substrate specificities of the acyltransferase (AT) domains, as well as the reductive loop domains identified within each module, are consistent with expectations from the structure of soraphen A. Genes were identified in the regions flanking the two soraphen synthase genes that are proposed to have roles in the biosynthesis of soraphen A. Downstream of the soraphen PKS genes is an O-methyltransferase (OMT) gene. Upstream of the soraphen PKS genes there is a gene encoding a reductase and a group of genes that are postulated to have roles in the synthesis of methoxymalonyl-acyl carrier protein (ACP). This unusual extender unit is proposed to be incorporated in two positions of the soraphen polyketide chain. One of the genes in this group contains distinct domains for an AT, an ACP, and an OMT.
authors.affiliation: Syngenta Biotechnology, Inc., Research Triangle Park, NC 27709, USA. james.ligon@syngenta.com
authors.forename: James
authors.initials: J
authors.lastname: Ligon
authors.forename: Steven
authors.initials: S
authors.lastname: Hill
authors.forename: James
authors.initials: J
authors.lastname: Beck
authors.forename: Ross
authors.initials: R
authors.lastname: Zirkle
authors.forename: István
authors.initials: I
authors.lastname: Molnár
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zawodny
authors.forename: Stephanie
authors.initials: S
authors.lastname: Money
authors.forename: Thomas
authors.initials: T
authors.lastname: Schupp
mesh_terms: D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D023061:Gene Order; D005798:Genes, Bacterial / Q000235:genetics; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism*; D007659:Ketones / Q000378:metabolism; D018942:Macrolides; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009231:Myxococcales / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D004269:DNA, Bacterial; D006571:Heterocyclic Compounds; D007659:Ketones; D018942:Macrolides; C086151:soraphen A