Coenzyme Biosynthesis in Archaea

辅酶是所有已知酶促反应中一半以上的必需组分。 因此，人们会认为辅酶生物合成的进化是生命早期进化过程中的一个中心事件。 尽管辅酶对生命系统的重要性，我们目前关于其生物合成的知识还远未完成。 在许多情况下，我们不知道其生物合成的确切途径和/或参与其生物合成的酶/基因。这个问题对于辅酶来说是非常严重的。 对于已知酶/基因的途径，越来越清楚的是，许多步骤是由非直链酶或与其他两个生命领域细菌和真核生物中存在的酶仅远亲的酶进行的。 由于不同辅酶的生物合成有许多共同的化学步骤，产甲烷菌辅酶的生物合成与常见细菌辅酶（如FAD，NAD，辅酶A等）的生物合成之间可能存在联系。由本基金资助的研究将通过继续在我的实验室开展工作来解决这些问题，以探索辅酶生物合成的以下方面：1）确定途径未知的酵母辅酶的生物合成途径，2）在酵母中建立基因，从而建立负责所选辅酶途径中各个步骤的酶，以及3）基于序列/序列分析来寻找参与辅酶生物合成途径的酶之间的进化关系。这些生物合成酶的结构同源性。这项研究将通过建立维生素/辅酶在当今生物体中的生物合成来探索代谢的进化发展。 由于这些维生素/辅酶对所有生物体都是必不可少的，因此了解维生素如何在居住在我们星球上的许多不同生物体中形成，可以让我们深入了解地球上以及宇宙中其他地方的生物代谢系统是如何进化的。

Coenzymes are essential components for more than half of all known enzymatic reactions. One would thus expect the evolution of the biosynthesis of coenzymes to have been a central event during the early evolution of life. Despite the importance of coenzymes to living systems, our current knowledge concerning their biosynthesis is far from complete. In many cases we do not know the exact pathways for their biosynthesis and/or the enzymes/genes involved in their biosynthesis. This problem is very acute for the Archaeal coenzymes. For the pathways in which the enzymes/genes are known, it is becoming increasingly clear that many of the steps are carried out either by non-orthologous enzymes or enzymes that are only distantly related to enzymes present in the other two Domains of life the Bacteria and the Eukarya. Because of many chemical steps common to the biosynthesis of different coenzymes, there may be connections between the biosynthesis of the methanogenic Archaeal coenzymes and the biosynthesis of the common Bacterial coenzymes such as FAD, NAD, coenzyme A, etc. Research funded by this grant will address these concerns by continuing the work in my laboratory to explore the following aspects of coenzyme biosynthesis: 1) determination of the biosynthetic pathway for the Archaeal coenzymes whose pathways are not known, 2) establishing the genes and thus the enzymes in the Archaea responsible for the individual steps in the pathways for selected coenzymes, and 3) searching for evolutionary relationships between the enzymes involved in coenzyme biosynthetic pathways based on sequence/structural homologies of these biosynthetic enzymes.The research to be undertaken by this grant will explore the evolutionary development of metabolism by establishing the biosynthesis of vitamins/coenzymes in present day organisms. Since these vitamins/coenzymes are essential for all living organisms, an understanding of how vitamins are formed in the many different organisms that inhabit our planet can be used to give us insight into how living metabolic systems evolved on earth and possibly in other places in the universe.