Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea.
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.
Donadio
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Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL 60064.
Katz
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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
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