Coenzyme Biosynthesis in Archaea

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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.