title: Analysis of the ambruticin and jerangolid gene clusters of Sorangium cellulosum reveals unusual mechanisms of polyketide biosynthesis.
abstract: Ambruticins and jerangolids are structurally related antifungal polyketides produced by Sorangium cellulosum strains. Comparative analysis of the gene clusters and characterization of compounds produced by gene knockout strains suggested hypothetical schemes for biosynthesis of these compounds. Polyketide synthase (PKS) architecture suggests that the pyran ring structure common to ambruticins and jerangolids forms by an intramolecular reaction on a PKS-bound intermediate. Disrupting ambM, encoding a discrete enzyme homologous to PKS C-methyltransferase domains, gave 15-desmethylambruticins. Thus, AmbM is required for C-methylation, but not pyran ring formation. Several steps in the post-PKS modification of ambruticin involve new enzymology. Remarkably, the methylcyclopropane ring and putative carbon atom excision during ambruticin biosynthesis apparently occur on the PKS assembly line. The mechanism probably involves a Favorskii rearrangement, but further work is required to elucidate these complex events.
authors.affiliation: Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, California 94545, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Julien
authors.forename: Zong-Qiang
authors.initials: ZQ
authors.lastname: Tian
authors.forename: Ralph
authors.initials: R
authors.lastname: Reid
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Reeves
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics*; D009231:Myxococcales / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000475:Alkenes; D018942:Macrolides; D011714:Pyrans; C098368:jerangolid A; C519141:jerangolid D; D048630:Polyketide Synthases; C014964:ambruticin