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Cloning and sequence analysis of the putative rifamycin polyketide synthase gene cluster from Amycolatopsis mediterranei
Authors:Thomas Schupp  Christiane Toupet  Nathalie Engel  Stephen Goff
Institution:Novartis Pharma AG, Core Technology Area, K-681.3.44, CH 4002 Basel, Switzerland;Novartis Crop Protection Inc., Biotechnology and Genomics Center, Research Triangle Park, NC, USA
Abstract:The 54-kbp Type I polyketide synthase gene cluster, most probably involved in rifamycin biosynthesis by Amycolatopsis mediterranei, was cloned in E. coli and completely sequenced. The DNA encodes five closely packed, very large open reading frames reading in one direction. As expected from the chemical structure of rifamycins, ten polyketide synthase modules and a CoA ligase domain were identified in the five open reading frames which contain one to three polyketide synthase modules each. The order of the functional domains on the DNA probably reflects the order in which they are used because each of the modules contains the predicted acetate or propionate transferase, dehydratase, and β-ketoacyl-ACP reductase functions, required for the respective step in rifamycin biosynthesis.
Keywords:Amycolatopsis mediterranei            Rifamycin  Ansamycin  Polyketide synthase  Polyketide synthase gene cluster  Cloning  Sequence analysis
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