Methyltransfer Reactions in the Reductive Acetyl-Coenzym A Pathway


Anaerobic bacteria and archaea use homologous enzymes to convert CO2 and H2 to acteyl-CoA and methane, which determine the global carbon cycle on earth since the dawn of life. We want to clarify (I) the mechanism of the reductive activator such as the function and mechanism of ATP hydrolysis and the role of dissociation of the CoFeSP-activator complex for electron transfer. The rate-determining step of the reaction needs to be determined, as well as the position of the electron-donating (2Fe2S) cluster domain in the complex. (II) Where the substrates and intermediates CO, CH3CO+, CH3+ and coenzyme A bind on the Ni-Ni-(4Fe4S) cluster of acetyl-CoA synthase is still unkwnown and we want to use the good quality of our crystals to gain a first look into the substrate binding place and mechanism. (III) We want to investigate the homologous enzymes from methanogenic archaea that, in contrast to the bacterial proteins, form an approximately 2,5 MDa complex, containing acetyl-CoA synthase, carbon monoxide dehydrogenase and CoFeSP. The reactions of the three enzymes are coordinated in the complex in an as yet unkwown way. Wjile bacterial CoFeSP is methylated by methyltetrahydrofolate-dependent methyltransferase, the CoFeSP homologs from methanogens can methylate itself using CH3-methanopterin as substrate. Comparing the enzymes of bacteria and archaea will give further insight into the early stages in the evolution of B12-dependent methyltransferases and the origin of methanogenesis and acetogenesis.


Principal Investigators
Dobbek, Holger Prof. Dr. rer. nat. (Details) (Structural Biology / Biochemistry)

Duration of Project
Start date: 11/2015
End date: 12/2020

Last updated on 2021-04-01 at 17:46