title: New insights into polyene macrolide biosynthesis in Couchioplanes caeruleus.
abstract: Couchioplanes caeruleus DSM43634 synthesises 67-121C, an aromatic heptaene macrolide that contains a mannosyl-mycosaminyl disaccharide. An improved draft genome sequence was used to obtain the biosynthetic gene cluster for this antifungal. Bioinformatic analysis of the polyketide synthase indicated that extension modules 7 and 8 contain A-type ketoreductase and dehydratase domains. These modules are therefore predicted to form cis double bonds. The deduced stereostructure of the 67-121C macrolactone is identical to that experimentally determined for the partricin subgroup of aromatic heptaenes. Some of these polyenes are N-methylated on the aminoacetophenone moiety. The C. caeruleus AceS protein was shown to methylate 4-aminoacetophenone and esters of 4-aminobenzoate, but not 4-aminobenzoate. This suggests that the substrate specificity of AceS prevents it from interfering with folate biosynthesis. The methyltransferase should be valuable for chemoenzymatic alkylation of compounds that contain aminobenzoyl moieties.
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland. patrick.caffrey@ucd.ie.
authors.forename: J
authors.initials: J
authors.lastname: Sheehan
authors.forename: C D
authors.initials: CD
authors.lastname: Murphy
authors.forename: P
authors.initials: P
authors.lastname: Caffrey
mesh_terms: D039903:Actinobacteria / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D053898:Biosynthetic Pathways; D019295:Computational Biology / Q000379:methods; D016680:Genome, Bacterial; D018942:Macrolides / Q000378:metabolism*; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics*; D008968:Molecular Conformation; D011090:Polyenes / Q000378:metabolism*; D011487:Protein Conformation; D000072417:Protein Domains; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D018942:Macrolides; D011090:Polyenes; D008780:Methyltransferases