Autotrophic growth: methylated carbon monoxide dehydrogenase as an intermediate of acetyl-CoA synthesis

A new pathway of autotrophic growth has been discovered in certain anaerobic bacteria in which acetyl-CoA is the product formed from CO/sub 2/ for initiation of anabolism rather than 3-phosphoglycerate as in the Calvin Cycle. CO/sub 2/ is reduced in combination with tetrahydrofolate to methyltetrahydrofolate (CH/sub 3/THF) and is the source of the CH/sub 3/ group. CO/sub 2/ or CO is the source of the carbonyl group. CO dehydrogenase (CODH), corrinoid enzyme, methyltransferase, ferredoxin and CODH disulfide reductase have been isolated from Clostridium thermoaceticum and shown to catalyze the synthesis of acetyl-CoA from CH/sub 3/THF, CO and CoA. The methyltransferase catalyzes transfer of the CH/sub 3/ group from CH/sub 3/THF to the corrinoid enzyme from which the methyl is transferred to CODH. CO is bound to the Ni of CODH forming a Ni-Fe-C center. When CO/sub 2/ is the source of carbon, H/sub 2/ and hydrogenase are required for reduction of the CO/sub 2/ by CODH. CODH disulfide reductase is required for the addition of CoA to the CODH (Pezacka, E. and Wood, H.G. J. Biol. Chem., in press). Then, CODH catalyzes the combination of the three groups forming acetyl-CoA. The authors have now succeeded in methylating CODH using /supmore » 14/CH/sub 3/I or /sup 14/CH/sub 3/-B/sub 12/. With the resulting /sup 14/CH/sub 3/-CODH, only CODH disulfide reductase is required for synthesis of (/sup 14/C)acetyl-CoA from CO and CoA. The amino acid sequence at the CH/sub 3/-site is being investigated.« less