GENETIC ANALYSIS OF MG-TETRAPYRROLE BIOSYNTHESIS

复杂的四吡咯生物合成途径负责 合成重要的代谢物，如维生素B12、血红素、胆红素和 叶绿素。从5-氨基酮戊酸到5-氨基酮戊酸途径的“共同主干” 原卟啉IX，由于以下事实而受到最大关注 许多遗传性疾病(门静脉症)是由 生产过量的血红素前体。临床表现： 过度生产这些中间产物的范围从简单的皮肤损伤到 精神错乱，到死。该途径的维生素B12分支有 最近也受到了相当大的关注。许多基因都涉及到 已在假单胞菌中鉴定出维生素B12的合成 在鼠伤寒沙门氏菌中。与关于亚铁血红素和亚铁血红素 维生素B12的合成，关于控制它的基因的信息很少 负责合成的镁-四吡咯支链的合成 叶绿素和细菌叶绿素。 在这项提案中，我们计划进行详细的生化和遗传 该菌生物合成镁四吡咯途径的分析 荚膜红杆菌。这包括(I)生物化学特性 生物合成途径中镁-四吡咯分支的酶，(Ii) 氧化还原反应的生化和遗传学特征 调节血红素、镁四吡咯表达的转录因子 和类胡萝卜素生物合成基因以及包括 光系统的光收集-II部分。(三)。 额外转录和转录后的特征 控制中间产品流动的监管因素 四氢吡咯生物合成途径的分支。(四)调查 聚球藻PCC6803生物合成镁-四吡咯 也将开始用于比较分析以及 真核生物镁-四吡咯生物合成模型系统。 对四吡咯生物合成途径的透彻理解有一些 超越学术哲学的广泛的实践影响 利息。其中包括一些明显的商业应用，例如 针对镁四吡咯途径中的酶的除草剂的设计， 以及过度生产四吡咯终端产品对健康的影响 维生素B12和亚铁血红素。同样不应忽视的是， 四苯并吡咯驱动的光合作用是捕获和 为活细胞提供能量，因此，它是最 这是我们技术世界的重要能源。

The complex tetrapyrrole biosynthetic pathway is responsible for synthesizing important metabolites such as vitamin B12, hemes, bilins and chlorophylls. The "common trunk" of the pathway from 5-aminolevulinate to protoporphyrin IX, has received the most 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 considerable attention as of late. Many genes involved in vitamin B12 synthesis have been identified in Pseudomonas dentrificans and in Salmonella typhimurium. In contrast to the information on heme and vitamin B12 synthesis, there is little information on genes which control synthesis of the Mg-tetrapyrrole branch which is responsible for synthesis of chlorophylls and bacteriochlorophylls. In this proposal we plan to perform detailed biochemical and genetic analysis of the Mg-tetrapyrrole biosynthetic pathway from the bacterium Rhodobacter capsulatus. This 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-tetrapyrrole and carotenoid biosynthesis genes as well as polypeptides that comprise the light harvesting-II portion of the photosystem. (iii). Characterization of additional transcriptional and post-transcriptional regulatory factors that controls the flow of intermediates through this branch of the tetrapyrrole biosynthetic pathway. (iv) Investigations on Mg-tetrapyrrole biosynthesis in the cyanobacterium Synechocystis PCC 6803 will also be initiated for use in a comparative analysis as well as a model system for Mg-tetrapyrrole biosynthesis in eukaryotes. A thorough understanding of the tetrapyrrole biosynthetic pathway has some far ranging practical implications beyond an academic philosophical interest. These include some obvious commercial applications, such as the design of herbicides that target enzymes in the Mg tetrapyrrole pathway, and the health implications of overproducing tetrapyrrole endproducts 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.