MICROBIAL METABOLISM OF REDUCED PHOSPHORUS COMPOUNDS

描述(由申请人提供)：拟议研究的长期目标是研究还原磷(P)化合物的生物合成和分解代谢所涉及的微生物代谢过程的分子、遗传和生化特征。众所周知，这些化合物在自然界中广泛存在，其中许多具有非常有用的性质，但我们对它们的新陈代谢的了解非常有限。在之前的研究过程中，我们分离到了许多具有氧化还原P化合物的新生化途径的微生物。此外，已知有许多其他生物通过未知的途径合成还原的P化合物。此外，有充分的证据表明，在微生物世界中，大量降低的磷代谢有待发现。探讨生物活性还原磷化合物的生物合成可能会提高我们生产这些具有医学和农业意义的产品的能力。此外，这些调查很可能导致发现新的生物活性还原P化合物。最后，磷是许多生态系统中的限制性营养物质。有人认为，磷的氧化还原反应可能在这一所需养分的生物有效性和全球循环中发挥重要作用。这项建议试图通过利用遗传、生物化学和分子方法来阐明特定还原磷化合物的生产和消费所涉及的代谢途径，以弥补对自然界中还原磷化合物知识的缺乏。这些实验的具体目的是：(1)表征大肠杆菌碱性磷酸酶史无前例的亚磷酸依赖的氢酶活性；(2)黄色黄杆菌次磷酸盐氧化新途径的遗传和生化表征；(3)各种链霉菌中膦酸类抗生素生物合成的分子、遗传和生化表征；(4)用于鉴定新型生物生产的膦酸类抗生素的分子筛选方法的开发和应用。

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.