Biosynthesis of Deazapurine-Containing Metabolites

描述(由申请人提供)：所有生物体都能产生许多在初级代谢过程中通常不需要的化合物，但它们发挥着重要的调节功能。这些次生代谢物已被每一种文明用来提高生命和治疗人类疾病。我们知道这些是激素、抗生素、抗肿瘤药物和抗病毒药物。由于这些代谢物如果产生过多，或者如果在不需要它们的情况下存在，则会损害细胞，因此它们的产生通常受到严格的监管。了解细胞如何合成和调节次生代谢物的产生是至关重要的，如果人们能够将它们用作人类治疗药物的话。地扎普林是由嘌呤衍生的次生代谢物。本提案概述了细菌生物合成含去氮嘌呤的次生代谢物的研究。我们的目标是利用基因组学、分子生物学和酶学的工具，形成这些代谢物是如何合成的框架，并探索这些分子生物合成所依据的化学转化。

DESCRIPTION (provided by applicant): All organisms produce a host of compounds that are generally not required in primary metabolic processes, but play important regulatory functions. These secondary metabolites have been exploited by every civilization to enhance life and cure human diseases. We know these as hormones, antibiotics, antitumor agents, and antivirals. Since these metabolites can harm cells if produced in excess, or if present when a need for them does not exist, their production is often strictly regulated. An understanding of how cells synthesize and regulate the production of secondary metabolites is essential if one is to be able to exploit them as human therapeutic agents. Deazapurines are secondary metabolites that are derived from purines. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by bacterIa. Our goal is to bring to fore the tools of genomics, molecular biology and enzymology to form the framework of how these metabolites are synthesized, and to exploring the chemical transformations that underlies the biosynthesis of these molecules.