CODH

CODH/ACS is an extremely oxygen-sensitive protein that has been found in anaerobic microbes. It also is one of the three known nickel iron-sulfur proteins. Some authors would consider that there are only two, since the CODH and ACS activities are tightly linked in many organisms. However, there is strong evidence that the ACS and CODH activities are associated with different protein subunits and the reactions that the two enzymes catalyze are quite different. CODH catalyzes a redox reaction and ACS catalyzes the nonredox condensation of a methyl group, a carbonyl group, and an organic thiol (coenzyme A). 

CODH and ACS are important from an evolutionary point of view. It has been considered that CODH/ACS are the extant survivors of a 3- to 4-billion-year-old process that could have given rise to the first metabolic reactions that eventually led to life on this planet. Possibly, it was involved in the first metabolic pathway (2, 107). 

Yagi laid the foundation for the enzymology of CODH when he discovered an enzymatic activity in sulfate-reducing bacteria that oxidizes CO to CO2 (118). Twenty-five years later, the first CODH was purified to homogeneity (119, 120). The homogeneous C. thermo-aceticum CODH was shown to contain 2 mol of nickel, 12 iron, 1 zinc, and 14 acid-labile inorganic sulfide per afS dimeric unit (120). 

The most important physiological role of CODH in the metabolism of acetogenic bacteria was unknown until 1985, when it was shown that the enzyme is bifunctional and has acetyl-CoA synthase activity (121). It was previously thought that acetyl-CoA was synthesized at the cobalt center of a vitamin-Bi2-containing protein. In the same paper, it was proposed that nickel is the active site of CO oxidation and acetyl-CoA synthesis. 

The properties of CODH/acetyl-CoA synthase are summarized in Table II. The enzyme has been isolated from eight species. There exist three types of CODH. One, which lacks nickel and acetyl-CoA synthase activity, contains a molybdopterin active site and will not be... 

Fractionation of a five-component system from C. thermoaceticum that catalyzes acetyl-CoA synthesis. CODH activity was in fraction F3. 

The adduct between CO and a nickel center in CODH identified by EPR spectroscopy. ... 

CODH from acetogens found to catalyze acetyl-CoA synthesis and nickel proposed to be the active site of CO oxidation and acetyl-CoA synthesis. CODH found to contain a heterometallic cluster consisting of nickel and iron that binds CO and proposed to be the active site of acetyl-CoA synthesis. Growth of acetogens on nitrate disables the acetyl-CoA pathway. ... 

Gene cluster encoding CODH/ACS, the CFeSP, and methyltransferase isolated and characterized. ... 

CODH and ACS shown to occur at discrete [Ni-X-Fe4S4] clusters, called Cluster C and Cluster A, respectively. ... 

Fig. 10. Milestones in the study of CODH/ACS. Important discoveries beginning with the postulate of a new CO2 fixation pathway.

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