title: Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea.
abstract: Localization of the enzymatic domains in the three multifunctional polypeptides from Saccharopolyspora erythraea involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin was determined by computer-assisted analysis. Comparison of the six synthase units (SU) from the eryA genes with each other and with mono- and multifunctional fatty acid and polyketide synthases established the extent of each beta-ketoacyl acyl-carrier protein (ACP) synthase, acyltransferase, beta-ketoreductase, ACP, and thioesterase domain. The extent of the enoyl reductase (ER) domain was established by detecting similarity to other sequences in the database. A segment containing the putative dehydratase (DH) domain in EryAII, with a potential active-site histidine residue, was also found. The finding of conservation of a portion of the DH-ER interdomain region in the other five SU, which lack these two functions, suggests a possible evolutionary path for the generation of the six SU.
authors.affiliation: Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: S
authors.initials: S
authors.lastname: Donadio
authors.forename: L
authors.initials: L
authors.lastname: Katz
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000737:chemistry / Q000378:metabolism; D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism; D004950:Esterases / Q000737:chemistry / Q000378:metabolism; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D016930:Saccharopolyspora / Q000201:enzymology*; D016415:Sequence Alignment
chemical_list: D000213:Acyl Carrier Protein; D009097:Multienzyme Complexes; C034277:6-deoxyerythronolide B; D004917:Erythromycin; D010088:Oxidoreductases; D007658:Ketone Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D000217:Acyltransferases; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D004950:Esterases; D006836:Hydro-Lyases