Does acetogenesis really require especially low reduction potential?

Acetogenesis is one of the oldest metabolic processes on Earth, and still has a major global significance. In this process, acetate is produced via the reduction and condensation of two carbon dioxide molecules. It has long been assumed that acetogenesis requires ferredoxin with an exceptionally low reduction potential of approximate to-500 mV in order to drive CO2 reduction to CO and the reductive carboxylation of acetyl-CoA to pyruvate. However, no other metabolic pathway requires electron donors with such low reduction potential. Is acetogenesis a special case, necessitating unique cellular conditions? In this paper, I suggest that it is not. Rather, by keeping CO as a bound metabolite, the CO-dehydrogenase-acetyl-CoA-synthase complex can couple the unfavorable CO2 reduction to CO with the favorable acetyl-CoA synthesis, thus enabling the former process to proceed using ferredoxin of moderate reduction potential of -400 mV. I further show that pyruvate synthesis can also take place using the same ferredoxins. In fact, the synthesis of pyruvate from CO2, methylated-protein-carrier and -400 mV ferredoxins is an energy-neutral process. These findings suggest that acetogenesis can take place at normal cellular redox state. Mechanistic coupling of reactions as suggested here can flatten energetic landscapes and diminish thermodynamic barriers and can be another role for enzymatic complexes common in nature and a useful tool for metabolic engineering. (C) 2012 Elsevier B.V. All rights reserved.