Uncovering the emergence of biocatalysis: structure-activity relationship of coenzyme A in the origin of life context – COASAR

Enzymes promote a great part of reactions in biological metabolism, often aided by cofactors which facilitate catalysis by binding to enzymes. Cofactors are involved in >60% of known enzymatic mechanisms and many of them can catalyse chemical reactions in the absence of enzymes. Several major cofactors may have been present in the Last Universal Common Ancestor, but their history could date earlier. It is possible that small-molecule cofactors played an important catalytic role during the early evolution of life on Earth, before the advent of ribosomal and enzymatic biocatalysis. The chemical structures of cofactors are universal across all of life. Still, it remains unknown how cofactors acquired these structures and what the origin of their biosynthesis is. The goal of this project is to study the functional rationale behind the structure of one of the most central cofactor, CoA. A prebiotic synthesis of CoA or its predecessor will be also explored in a way that mimics biosynthesis.