MICROBIAL METABOLISM OF REDUCED PHOSPHORUS COMPOUNDS

描述（由申请人提供）：拟议研究的长期目标是参与生物合成和还原磷(P)化合物分解代谢的微生物代谢过程的分子，遗传和生化表征。众所周知，这些化合物在自然界中普遍存在，其中许多具有非常有用的特性，但我们对其代谢的了解非常有限。在之前的研究过程中，我们分离了许多具有新的生化途径氧化还原P化合物的微生物。此外，已知多种其他生物通过未知途径合成还原性P化合物。此外，有充分的证据表明，在微生物世界中，大量的磷代谢减少有待发现。探索生物活性还原性磷化合物的生物合成可以提高我们生产这些医学和农业上重要产品的能力。此外，这些调查很可能导致发现新的生物活性的还原价磷化合物。最后，磷在许多生态系统中是限制性养分。研究表明，磷的氧化还原反应可能在这种必需营养物的生物利用度和全球循环中起重要作用。本提案旨在通过利用遗传、生化和分子方法来阐明所选择的还原价磷化合物的产生和消耗所涉及的代谢途径，来弥补自然界中还原价磷化合物知识的缺乏。这些实验的具体目的是：(1)研究大肠杆菌碱性磷酸酶中前所未有的磷酸依赖氢化酶活性，(2)黄黄杆菌中次磷酸酯氧化新途径的遗传和生化特征，(3)各种链霉菌中磷酸盐抗生素生物合成的分子、遗传和生化特征，以及(4)分子筛选方法的开发和应用，以鉴定新型、生物产生的磷酸盐抗生素。

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.