A corrinoid-dependent catabolic pathway for growth of a Methylobacterium strain with chloromethane

Methylobacterium sp. strain CM4, an aerobic methylotrophic alpha-proteobact erium, is able to grow with chloromethane as a carbon and energy source. Mu tants of this strain that still grew with methanol, methylamine, or formate , but were unable to grow with chloromethane, were previously obtained by m iniTn5 mutagenesis, The transposon insertion sites in six of these mutants mapped to two distinct DNA fragments, The sequences of these fragments, whi ch extended over more than 17 kb, were determined. Sequence analysis, mutan t properties, and measurements of enzyme activity in cell-free extracts all owed the definition of a multistep pathway for the conversion of chlorometh ane to formate, The methyl group of chloromethane is first transferred by t he protein CmuA (cmu: chloromethane utilization) to a corrinoid protein, fr om where it is transferred to H(4)folate by CmuB, Both CmuA and CmuB displa y sequence similarity to methyltransferases of methanogenic archaea, In its C-terminal part, CmuA is also very similar to corrinoid-binding proteins, indicating that it is a bifunctional protein consisting of two domains that are expressed as separate polypeptides in methyl transfer systems of metha nogens, The methyl group derived from chloromethane is then processed by me ans of pterine-linked intermediates to formate by a pathway that appears to be distinct from those already described in Methylobacterium. Remarkable f eatures of this pathway for the catabolism of chloromethane thus include th e involvement of a corrinoid-dependent methyltransferase system for dehalog enation in an aerobe and a set of enzymes specifically involved in funnelin g the C1 moiety derived from chloromethane into central metabolism.