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Aromatic Metabolism: A Web of Biochemical Networks

芳香代谢：生化网络之网

基本信息

批准号：
7050070
负责人：
ROY A JENSEN
金额：
$ 5万
依托单位：
INDEPENDENT SCHOLAR--JENSEN, ROY A.
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-01 至 2007-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The biochemical pathway for biosynthesis of aromatic amino acids is widespread in prokaryotes, eukaryotic microorganisms, and in higher plants but is absent in mammalian organisms. Therefore, the multiplicity of enzymes that are utilized by this pathway are apt targets for the design of antimicrobial and herbicidal compounds, which have no target in man and other mammals. Furthermore, there is an increasing recognition of the enormous diversity between organisms with respect to the details of aromatic metabolism and the context of interface with other metabolic networks. Thus, there are many possibilities for selective approaches against pathogens that will not harm beneficial microorganisms. In addition, the metabolism of aromatic compounds in nature is of particular interest to man because it is a source of numerous natural products that are useful (e.g., antibiotics, pigments, etc.) or harmful (e.g., toxins). Two manuscripts will be prepared that elucidate in scholarly and comprehensive detail the biochemical mechanisms and enzymological features of aromatic metabolism. The latter information will be integrated into a comparative and evolutionary context and will be guided by a genomic and bioinformatic perspective. A nomenclature will be developed that has a rational basis and is suitable for comparative analysis. A larger gestalt of metabolic networking will be elucidated by inclusion of interlocking biochemical pathways, e.g., the direct relationship between sedne and tryptophan synthesis, as well as the more remote relationships that also include folate biosynthesis (via 4-aminobenzoate), pyridoxine biosynthesis, and histidine biosynthesis. A web site will be created to allow public access to the information and analysis as it is organized and will be designed to facilitate a long-term process that at maturation in 3 years will justify a long-term objective of securing a database that can be maintained, improved and progressively expanded to other metabolic networks.

描述（由申请人提供）：芳香族氨基酸生物合成的生化途径广泛存在于原核生物、真核微生物和高等植物中，但在哺乳动物中不存在。因此，该途径所利用的多种酶是设计抗微生物和除草化合物的合适靶标，而这些化合物在人类和其他哺乳动物中没有靶标。此外，越来越多的认识到有机体之间的巨大多样性方面的芳香代谢的细节和与其他代谢网络的接口的背景。因此，有许多选择性方法对抗病原体，而不会伤害有益的微生物。此外，自然界中芳香族化合物的代谢是人类特别感兴趣的，因为它是许多有用的天然产物（例如，抗生素、色素等）或有害的（例如，毒素）。将准备两份手稿，阐明在学术和全面详细的生化机制和芳香代谢的酶学特征。后者的信息将被整合到一个比较和进化的背景下，并将由基因组和生物信息学的角度来指导。将制定一个具有合理基础并适合于比较分析的术语。代谢网络的一个更大的完形将通过包含连锁的生化途径来阐明，例如，sedne和色氨酸合成之间的直接关系，以及更远的关系，还包括叶酸生物合成（通过4-氨基苯甲酸）、吡哆醇生物合成和组氨酸生物合成。将建立一个网站，使公众能够获得信息和分析，因为它是有组织的，并将被设计为促进一个长期的过程，在3年内成熟将证明一个长期的目标，确保数据库，可以维护，改进和逐步扩大到其他代谢网络。