Coproheme - a naturally occuring Cofactor?

Heme enzymes are responsible for a wide variety of reactions and functions in living organisms. Heme biosynthesis in prokaryotes follows either the coproporphyrin-dependent or the siroheme-dependent metabolic pathway. In both cases, coproheme is the substrate for the final step of biosynthesis. In *Desulfovibrio desulfuricans*, it was found that the storage protein bacterioferritin stores large amounts of coproheme. These and other data in the literature suggest that coproheme could be another naturally occurring cofactor. We will investigate this lead to expand our understanding of biochemical metabolic pathways. The hypothesis is that coproheme is a naturally occurring cofactor in prokaryotic organisms. Coproheme has been shown to act as a redox-active substrate for an enzyme (coproheme decarboxylase). In this project, we will go beyond this reaction and test whether some organisms have evolved to prefer coproheme over heme b. Selected, well-studied heme enzymes reconstituted with coproheme are being studied biochemically and biophysically. This allows us to conduct a comparative assessment of the catalytic potential of coproheme enzymes. In addition, other heme enzymes from organisms that utilize the siroheme or coproporphyrin-dependent metabolic pathway are being studied in their coproheme-bound state. Furthermore, we will use computer-aided methods to search for previously unidentified coproheme-binding proteins. If this hypothesis is confirmed, we will have to rewrite the biochemistry textbooks. This basic research project will help us understand the structure-function relationships of these enzyme classes and provide important insights into the necessary conditions for efficient catalysis. Coproheme-bound enzymes are potentially of interest for biotechnological applications in industry and medicine.