Genetic Analysis of Mg-tetrapyrrole Biosynthesis

描述(申请人提供)：四吡咯生物合成途径为 负责合成重要的代谢物，如维生素B12，血红素， 胆红素和叶绿素。小路的“共同主干”，来自 5-氨基酮戊酸转化为原卟啉IX，由于 一些遗传性疾病(门静脉症)是由 生产过量的血红素前体。产力过剩的临床表现 这些中间体的范围从简单的皮肤损伤到精神障碍，再到 死亡。该途径的维生素B12分支最近也受到了关注 假单胞菌维生素B12合成相关基因的研究 脱氮杆菌和鼠伤寒沙门氏菌。 与关于血红素和维生素B12合成的丰富信息相比， 关于镁-四吡咯系列化合物的合成的信息刚刚出现 叶绿素。在这份提案中，我们概述了执行详细计划 镁-四氢吡咯生物合成途径的生化和遗传分析。 这项分析包括：(I)来自 生物合成途径中的镁-四吡咯分支，(Ii)生化和 氧化还原反应转录因子的基因特征 调节血红素、四氢镁的表达和类胡萝卜素的生物合成 基因，以及组成捕光-II部分的多肽 光系统。 对四吡咯生物合成途径的透彻理解还有很长的路要走。 范围广泛的实际意义，例如针对目标的除草剂的设计 镁四吡咯途径中的酶及其对健康的影响 过量生产四吡咯终端产品，如维生素B12和血红素。它应该是 同样不可忽视的是，四氢吡咯驱动的光合作用是主要的 获取能量并为活细胞提供能量的途径，因此，它 是我们技术世界中最重要的能源来源。

DESCRIPTION (provided by applicant): The tetrapyrrole biosynthetic pathway is responsible for synthesizing important metabolities such as vitamin B12, hemes, bilins and chlorophylls. The "common trunk" of the pathway, from 5-aminolevulinate to protoporphyrin IX, has received much attention owing to the fact that a number of heredity diseases (porphyrias) are caused by the overproduction of heme precursors. Clinical manifestations of overproducing these intermediates range from simple skin lesions, to psychotic disorders, to death. The vitamin B12 branch of the pathway has also received recent attention genes involved in vitamin B12 synthesis characterized from Pseudomonas denitrificans and in Salmonella typhimurium. In contrast to the wealth of information on heme and vitamin B12 synthesis, information is just emerging on the synthesis of the Mg-tetrapyrrole family of chlorophylls. In this proposal, we outline plans to perform detailed biochemical and genetic analysis of the Mg-tetrapyrrole biosynthetic pathway. This analysis includes (i) biochemical characterization of enzymes from the Mg-tetrapyrrole branch of the biosynthetic pathway, (ii) biochemical and genetic characterization of a redox responding transcription factor that regulates expression of heme, Mg-tetrapyrroles and carotenoid biosynthesis genes, as well as polypeptides that comprise the light harvesting-II portion of the photosystem. A thorough understanding of the tetrapyrrole biosynthetic pathway has some far ranging practical implications, such as the design of herbicides that target enzymes in the Mg tetrapyrrole pathway, and the health implications of overproducing tetrapyrrole end-products such as vitamin B12 and heme. It should also not be overlooked that tetrapyrrole driven photosynthesis is the primary route of capturing and supplying energy to living cells and, consequently, it is the most important source of energy in our technological world.