Identification of coenzyme M biosynthetic 2-phosphosulfolactate phosphatase - A member of a new class of Mg2+-dependent acid phosphatases

Coenzyme M (CoM; 2-mercaptoethanesulfonic acid) is the terminal methyl carr ier in methanogenesis. Methanogenic archaea begin the production of this es sential cofactor by sulfonating phosphoenolpyruvate to form 2-phospho-3 -su lfolactate. After dephosphorylation, this precursor is oxidized, decarboxyl ated and then reductively thiolated to form CoM. A thermostable phosphosulf olactate phosphohydrolase (EC 3.1.3.-) catalyzing the second step in CoM bi osynthesis, was identified in the hyperthermophilic euryarchaeon Methanococ cus jannaschii. The predicted ORF MJ1140 in the genome of M. jannaschii enc odes ComB, a Mg(2+-)dependent acid phosphatase that is specific for 2-hydro xycarboxylic acid phosphate esters. Recombinantly expressed purified ComB e fficiently hydrolyzes rac-2-phosphosulfolactate, (S)-2-phospholactate, phos phoglycolate and both enantiomers of 2-phosphomalate. In contrast to previo usly studied phosphoglycolate phosphatases, ComB has a low pH optimum for a ctivity, a narrow substrate specificity and an amino acid sequence dissimil ar to any biochemically characterized protein. Like other phosphatases that function via covalent phosphoenzyme intermediates, ComB can catalyze a tra nsphosphorylation reaction. Homologs of comB are identified in all availabl e cyanobacterial genome sequences and in genomes from phylogenetic ally div erse bacteria and archaea; most of these organisms lack homologs of other C oM biosynthetic genes. The broad and disparate distribution of comB homolog s suggests that the gene has been recruited frequently into new metabolic p athways.