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还原磷（P）化合物生物合成和催化的微生物代谢过程的分子、遗传和生物化学表征。已知这些化合物在自然界中普遍存在，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。在以前的研究过程中，我们分离出许多微生物与新的生化途径氧化还原磷化合物。此外，已知多种其他生物通过未知途径合成还原磷化合物。此外，有充分的证据表明，丰富的减少磷代谢等待发现在微生物世界。探究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医学和农业重要产品的能力。此外，这些调查很可能导致新的生物活性还原磷化合物的发现。最后，P是许多生态系统中的限制性营养素。磷的氧化还原反应可能在这种必需营养素的生物有效性和全球循环中发挥重要作用。该提案旨在弥补知识的缺乏，在自然界中的还原磷化合物，利用遗传，生物化学和分子的方法来阐明参与生产和消费的选定的还原磷化合物的代谢途径。这些实验的具体目的是：（1）表征大肠杆菌碱性磷酸酶的前所未有的亚磷酸盐依赖性氢化酶活性，（2）黄曲霉中次磷酸盐氧化的新途径的遗传和生物化学表征，（3）各种链霉菌中膦酸盐抗生素生物合成的分子、遗传和生物化学表征，以及（4）分子筛选方法的开发和应用，用于鉴定新的生物产生的膦酸酯抗生素。

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.