Biosynthesis of deazapurine-containing metabolites

描述（由申请人提供）：所有生物体都会产生大量化合物，这些化合物通常在初级代谢过程中不需要，但发挥重要的调节功能。每个文明都利用这些次生代谢物来增强生命和治疗人类疾病。我们知道它们是激素、抗生素、抗肿瘤药物和抗病毒药物。由于这些代谢物如果过量产生或在不需要它们时存在会损害细胞，因此它们的产生通常受到严格监管。如果要将细胞用作人类治疗剂，那么了解细胞如何合成和调节次生代谢物的产生至关重要。脱氮嘌呤是源自嘌呤的次级代谢物，人们对它们在细胞中如何合成知之甚少。该提案概述了链霉菌生物合成含氮杂嘌呤的次级代谢产物的研究。我们的目标是突出基因组学、分子生物学和酶学工具，形成这些代谢物合成的框架，并开始探索这些分子生物合成基础的化学过程。

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 and little is known about how they are synthesized in the cell. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by Streptomyces. 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 begin the process of exploring the chemistry that underlies the biosynthesis of these molecules.