MICROBIAL METABOLISM OF REDUCED PHOSPHORUS COMPOUNDS

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DESCRIPTION (provided by applicant): The long-term objective of the proposed research is the molecular, genetic and biochemical characterization of microbial metabolic processes involved in biosynthesis and catabolism of reduced phosphorus (P) compounds. These compounds are known to be prevalent in nature and many possess extremely useful properties, yet our knowledge of their metabolism is very limited. During the course of previous studies we isolated numerous microorganisms with novel biochemical pathways for oxidation of reduced P compounds. In addition, a variety of other organisms are known to synthesize reduced P compounds via unknown pathways. Moreover, there is ample evidence suggesting that a wealth of reduced P metabolism awaits discovery in the microbial world. Inquiry into the biosynthesis of bioactive reduced P compounds may improve our ability to produce these medically and agriculturally important products. Moreover, these inquiries are likely to result in the discovery of new bioactive reduced P compounds. Finally, P is the limiting nutrient in many ecosystems. It has been suggested that redox reactions of phosphorus may play an important role in the bio-availability and global cycling of this required nutrient. This proposal seeks to remedy the dearth of knowledge regarding reduced P compounds in nature by utilizing genetic, biochemical and molecular approaches to elucidate the metabolic pathways involved in production and consumption of selected reduced P compounds. The specific aims of these experiments are: (1) to characterize the unprecedented phosphite-dependent hydrogenase activity of Escherichia coli alkaline phbsphatase, (2) the genetic and biochemical characterization of novel pathway for hypophosphite oxidization in Xanthobacter flavus, (3) the molecular, genetic and biochemical characterization of phosphonate antibiotic biosynthesis in various Streptomyces species, and (4) the development and application of molecular screening approaches for the identification of novel, biologically produced, phosphonate antibiotics.