title: Biosynthesis of the erythromycin macrolactone and a rational approach for producing hybrid macrolides.
abstract: The three eryA genes involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin in Saccharopolyspora erythraea, appear to be organized in a single transcriptional unit on the basis of the results of gene disruption experiments. An insertion sequence-like element of lower G + C content separates eryAI from eryAII. The organization of the enzymatic domains present in the eryA-encoded multifunctional polypeptides, determined by computer-assisted analysis, is presented. This has enabled the determination of a putative dehydratase domain. A rational approach for producing novel macrolides by introducing selected changes in polyketide synthase genes is outlined. The isolation of a lactone intermediate resulting from an early synthesis step in macrolactone formation is also presented.
authors.affiliation: Corporate Molecular Biology Project, Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: S
authors.initials: S
authors.lastname: Donadio
authors.forename: M J
authors.initials: MJ
authors.lastname: Staver
authors.forename: J B
authors.initials: JB
authors.lastname: McAlpine
authors.forename: S J
authors.initials: SJ
authors.lastname: Swanson
authors.forename: L
authors.initials: L
authors.lastname: Katz
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004917:Erythromycin / Q000096:biosynthesis*; D005798:Genes, Bacterial; D005818:Genetic Engineering / Q000379:methods; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics; D016930:Saccharopolyspora / Q000235:genetics*
chemical_list: D009097:Multienzyme Complexes; D004917:Erythromycin