Methyltransfer Reactions in the Reductive Acetyl-Coenzyme a Pathway

The reductive acetyl-coenzyme A pathway allows several strictly anaerobically living bacteria and archaea to autothropically fix CO2. The final steps in the reductive acetyl-CoA pathway comprise the action of three highly conserved proteins, namely methyl-tetrahydrofolate:CoFeSP methyltransferase (MeTr), acetyl-CoA synthase (ACS) and the corrinoid/iron-sulfur protein (CoFeSP). CoFeSP bridges the two branches of the reductive acetyl-CoA pathway by accepting a methyl-group from MeTr in the Co(I) oxidation state and donating it to the Ni,Ni-[4Fe-4S] cluster of ACS from CH3-Co(III). The latter methyl transfer is unique and is the only known transfer of a methyl group between two metal sites (Co and Ni) in biology. Adventitious oxidation of Co(I) to Co(II) inactivates CoFeSP and needs a reductive reactivation by external electron sources. An open-reading-frame in the acs gene cluster codes for a protein with homology to the recently discovered ATP-dependent activators of corrinoid containing enzymes (RACE proteins), making the likely physiological reductant of Co2+FeSP. Our aim is to study the mechanism of the four individual proteins, determine whether the putative RACE proteins reacts with CoFeSP and understand how complexation between CoFeSP with MeTr (MeTr:Co1+FeSP), with the putative RACE protein (RACE:Co2+FeSP) and ACS (ACS:CH3-Co3+FeSP) is regulated.