Efficient catalysts for CO2 reduction are urgently needed in order to envision a circular economy that can rid humanity of its dependence on fossil fuels. Nature has since the beginning of life on Earth evolved several enzymes that can catalyze this reaction and one of those is Ni, Fe-carbon monoxide dehydrogenase (Ni, Fe-CODH) that catalyzes the reversible conversion of CO/CO2. (1) Ni, Fe-CODH is challenging to isolate in an active form and only a few examples have been thoroughly characterized. Previous bioinformatic studies have shown that there are several clades of the Ni, Fe-CODH phylogenetic tree that remain unexplored (2, 3) and initial results by us (unpublished) and others (4) indicate that some of these clades may have evolved away from the native CODH function of CO/CO2 conversion, putting their classification as CODHs into question.
We have studied the biodiversity of Ni, Fe-CODHs through a bioinformatic approach where our focus does not only lie on the CODH encoding genes but also on their genomic neighbourhood in order to gain insight into their natural function. We have also investigated the probability for co-occurrence of CODHs from different clades in the same organism to unravel any kind of inter-clade dependence. Based on this bioinformatic study, we have isolated novel CODHs from unexplored clades and characterized them using an array of biochemical and biophysical methods such as EPR and Cryo-EM/X-ray crystallography. Results show that the diversity with regards to activity and metallocofactor structure is more diverse than previously believed.
In conclusion, our findings have expanded our knowledge of Ni, Fe-CODH biodiversity and have opened up new possibilities for detailed studies of less explored areas of the phylogenetic tree.