InterPro domain: IPR010061

Methylmalonate-semialdehyde dehydrogenase (MMSDH, 1.2.1.27 ) catalyses the irreversible NAD+- and CoA-dependent oxidative decarboxylation of methylmalonate semialdehyde to propionyl-CoA. Methylmalonate-semialdehyde dehydrogenase has been characterised in both prokaryotes [ 1 , 2 ] and eukaryotes [ 3 ], functioning as a mammalian tetramer and a bacterial homodimer. Although similar in monomeric molecular mass and enzymatic activity, the N-terminal sequence in Pseudomonas aeruginosa does not correspond with the N-terminal sequence predicted for rat liver. Sequence homology to a variety of prokaryotic and eukaryotic aldehyde dehydrogenases places MMSDH in the aldehyde dehydrogenase (NAD+) superfamily making MMSDH's CoA requirement unique among known ALDHs. Methylmalonate semialdehyde dehydrogenase is closely related to betaine aldehyde dehydrogenase, 2-hydroxymuconic semialdehyde dehydrogenase, and class 1 and 2 aldehyde dehydrogenase [ 4 ].

In most cases these enzymes are involved in valine metabolism, but Gram-positive bacteria, such as Bacillus, contain a distinct subset. This subset of enzymes is encoded in an iol operon and is apparently involved in myo-inositol catabolism, converting malonic semialdehyde to acetyl CoA ad CO2 [ 4 ].

1. Characterization of the mmsAB operon of Pseudomonas aeruginosa PAO encoding methylmalonate-semialdehyde dehydrogenase and 3-hydroxyisobutyrate dehydrogenase. J. Biol. Chem. 267, 13585-92
2. Cloning and characterization of a gene (msdA) encoding methylmalonic acid semialdehyde dehydrogenase from Streptomyces coelicolor. J. Bacteriol. 178, 490-5
3. CoA-dependent methylmalonate-semialdehyde dehydrogenase, a unique member of the aldehyde dehydrogenase superfamily. cDNA cloning, evolutionary relationships, and tissue distribution. J. Biol. Chem. 267, 19724-9
4. Organization and transcription of the myo-inositol operon, iol, of Bacillus subtilis. J. Bacteriol. 179, 4591-8