Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin |
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| Institution: | 1. Department of Physiology and Pharmacology and Health Ageing Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan;2. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan;3. Department of Anesthetics, Chang Gung Memorial Hospital at Lin-Kou and College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan;4. Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan;1. Genome Informatics Research Group, Bionivid Technology Pvt Ltd., Bangalore 560043, India;2. Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata 700064, India |
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| Abstract: | Mithramycin (Mtm) is an aromatic polyketide which shows antibacterial and antitumor activity. From a chromosomal cosmid library of Streptomyces argillaceus, a Mtm producer, a clone (cosAR7) was isolated by homology to the actI/III region of S. coelicolor and the strDEM genes of S. griseus. From this clone, a 5.3-kb DNA region was sequenced and found to encode six open reading frames (designated as mtmQXPKSTI), five of them transcribed in the same direction. The deduced products of five of these genes resembled components of type-II polyketide synthases. The mtm genes would code for an aromatase (mtmQ), a polypeptide of unknown function (mtmX), a β-ketoacylsynthase (mtmP) and a related ‘chain length factor’ (mtmK), an acyl carrier protein (mtmS) and a β-ketoreductase (mtmT1). The involvement of this gene cluster in Mtm biosynthesis was demonstrated by the Mtm non-producing phenotype of mutants generated in two independent insertional inactivation experiments. |
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