5,10-Methylenetetrahydrofolate Reductases: Iron-Sulfur-Zinc Flavoproteins of Two Acetogenic Clostridia

5,10-Methylenetetrahydrofolate reductase catalyzes the two electron reduction of 5,10-niethylenetetrahydrofolate (CH2-H4folate) to 5-methyltetrahydrofolate (CH3-H4folate). Methylene-H4folate reductases have been purified from two acetogenic bacteria, the mesophile Clostridium formicoaceticum and the thermophile Clostridium thermoaceticum. Both enzymes are iron-sulfur-zinc flavoproteins, but, as is detailed in this presentation, they differ in several properties. Methylene-H4folate reductases from the acetogenic bacteria are oxygen sensitive. The oxygen sensitivity of the reductases is in contrast to other H4folate dependent enzymes including the formyl-H4foIate synthetases, methenyl-H4folate cyclohydrolases, and methylene-H4folate dehydrogenases from C. thermoaceticum and C. formicaceticum. Methylene-H4folate reductases are important enzymes in the newly discovered pathway of the synthesis of acetyl-CoA from CO2 in acetogenic bacteria. In the acetogens, the reduction of methylene-H4folate is part of a series of reactions which takes CO2 via formate, formyl-H4folate, methenyl-H4folate, and methylene-H4folate to methyl-H4folate. The latter is the source of the methyl group of the synthesis of acetyl-CoA.