Novel formaldehyde-activating enzyme in Methylobacterium extorquens AM1 required for growth on methanol

Formaldehyde is toxic for all organisms from bacteria to humans due to its reactivity with biological macromolecules. Organisms that grow aerobically on single-carbon compounds such as methanol and methane face a special chal lenge in this regard because formaldehyde is a central metabolic intermedia te during methylotrophic growth. In the alpha -proteobacterium Methylobacte rium extorquens AML, we found a previously unknown enzyme that efficiently catalyzes the removal of formaldehyde: it catalyzes the condensation of for maldehyde and tetrahydromethanopterin to methylene tetrahydromethanopterin, a reaction which also proceeds spontaneously, but at a lower rate than tha t of the enzyme-catalyzed reaction. Formaldehyde-activating enzyme (Fae) wa s purified from M. extorquens AM1 and found to be one of the major proteins in the cytoplasm. The encoding gene is located within a cluster of genes f or enzymes involved in the further oxidation of methylene tetrahydromethano pterin to CO2. Mutants of M. extorquens AM1 defective in Fae were able to g row on succinate but not on methanol and were much more sensitive toward me thanol and formaldehyde. Uncharacterized orthologs to this enzyme are predi cted to be encoded by uncharacterized genes from archaea, indicating that t his type of enzyme occurs outside the methylotrophic bacteria.