Involved in the assimilation of dimethylsulphoniopropionate (DMSP), an important compound in the fixation of carbon in marine phytoplankton, by catalyzing both the hydration and the hydrolysis of 3-(methylthio)acryloyl-CoA (MTA-CoA) to acetaldehyde, CO2, MeSH, and CoA. •

MTQDVTSGYSNLDLDLRDNGVCVVTLNRPDKRNALDVATIEELVTFFSTAHRKGVRAVVL TGAGDHFCAGLDLVEHWKADRSADDFMHVCLRWHEAFNKMEYGGVPIIAALRGAVVGGGL ELASAAHLRVMDQSTYFALPEGQRGIFTGGGATIRVSDMIGKYRMIDMILTGRVYQGQEA ADLGLAQYITEGSSFDKAMELADKIASNLPLTNFAICSAISHMQNMSGLDAAYAEAFVGG IVNTQPAARERLEAFANKTAARVRPNS271

	PMID	Title & Author	Abstract	Year
0	21562561	Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria. eisch CR, Stoudemayer MJ, Varaljay VA, Amster IJ, Moran MA, Whitman WB.	Dimethylsulphoniopropionate (DMSP) accounts for up to 10% of carbon fixed by marine phytoplankton in ocean surface waters, producing an estimated 11.7-103 Tmol S per year, most of which is processed by marine bacteria through the demethylation/demethiolation pathway. This pathway releases methanethiol (MeSH) instead of the climatically active gas dimethylsulphide (DMS) and enables marine microorganisms to assimilate the reduced sulphur. Despite recognition of this critical microbial transformation for over two decades, the biochemical pathway and enzymes responsible have remained unidentified. Here we show that three new enzymes related to fatty acid β-oxidation constitute the pathway that assimilates methylmercaptopropionate (MMPA), the first product of DMSP demethylation/demethiolation, and that two previously unknown coenzyme A (CoA) derivatives, 3-methylmercaptopropionyl-CoA (MMPA-CoA) and methylthioacryloyl-CoA (MTA-CoA), are formed as novel intermediates. A member of the marine roseobacters, Ruegeria pomeroyi DSS-3, requires the MMPA-CoA pathway for MMPA assimilation and MeSH production. This pathway and the ability to produce MeSH from MMPA are present in diverse bacteria, and the ubiquitous SAR11 clade bacterium Pelagibacter ubique possesses enzymes for at least the first two steps. Analysis of marine metagenomic data indicates that the pathway is widespread among bacterioplankton in the ocean surface waters, making it one of the most important known routes for acquisition of reduced carbon and sulphur by surface ocean heterotrophs.	2011
1	30677184	Mechanistic insight into 3-methylmercaptopropionate metabolism and kinetical regulation of demethylation pathway in marine dimethylsulfoniopropionate-catabolizing bacteria. Shao X, Cao HY, Zhao F, Peng M, Wang P, Li CY, Shi WL, Wei TD, Yuan Z, Zhang XH, Chen XL, Todd JD, Zhang YZ.	The vast majority of oceanic dimethylsulfoniopropionate (DMSP) is thought to be catabolized by bacteria via the DMSP demethylation pathway. This pathway contains four enzymes termed DmdA, DmdB, DmdC and DmdD/AcuH, which together catabolize DMSP to acetylaldehyde and methanethiol as carbon and sulfur sources respectively. While molecular mechanisms for DmdA and DmdD have been proposed, little is known of the catalytic mechanisms of DmdB and DmdC, which are central to this pathway. Here, we undertake physiological, structural and biochemical analyses to elucidate the catalytic mechanisms of DmdB and DmdC. DmdB, a 3-methylmercaptopropionate (MMPA)-coenzyme A (CoA) ligase, undergoes two sequential conformational changes to catalyze the ligation of MMPA and CoA. DmdC, a MMPA-CoA dehydrogenase, catalyzes the dehydrogenation of MMPA-CoA to generate MTA-CoA with Glu435 as the catalytic base. Sequence alignment suggests that the proposed catalytic mechanisms of DmdB and DmdC are likely widely adopted by bacteria using the DMSP demethylation pathway. Analysis of the substrate affinities of involved enzymes indicates that Roseobacters kinetically regulate the DMSP demethylation pathway to ensure DMSP functioning and catabolism in their cells. Altogether, this study sheds novel lights on the catalytic and regulative mechanisms of bacterial DMSP demethylation, leading to a better understanding of bacterial DMSP catabolism.	2019
2	28469605	Evolution of Dimethylsulfoniopropionate Metabolism in Marine Phytoplankton and Bacteria. Bullock HA, Luo H, Whitman WB.	The elucidation of the pathways for dimethylsulfoniopropionate (DMSP) synthesis and metabolism and the ecological impact of DMSP have been studied for nearly 70 years. Much of this interest stems from the fact that DMSP metabolism produces the climatically active gas dimethyl sulfide (DMS), the primary natural source of sulfur to the atmosphere. DMSP plays many important roles for marine life, including use as an osmolyte, antioxidant, predator deterrent, and cryoprotectant for phytoplankton and as a reduced carbon and sulfur source for marine bacteria. DMSP is hypothesized to have become abundant in oceans approximately 250 million years ago with the diversification of the strong DMSP producers, the dinoflagellates. This event coincides with the first genome expansion of the Roseobacter clade, known DMSP degraders. Structural and mechanistic studies of the enzymes of the bacterial DMSP demethylation and cleavage pathways suggest that exposure to DMSP led to the recruitment of enzymes from preexisting metabolic pathways. In some cases, such as DmdA, DmdD, and DddP, these enzymes appear to have evolved to become more specific for DMSP metabolism. By contrast, many of the other enzymes, DmdB, DmdC, and the acrylate utilization hydratase AcuH, have maintained broad functionality and substrate specificities, allowing them to carry out a range of reactions within the cell. This review will cover the experimental evidence supporting the hypothesis that, as DMSP became more readily available in the marine environment, marine bacteria adapted enzymes already encoded in their genomes to utilize this new compound.	2017
3	21886640	Bacterial Catabolism of Dimethylsulfoniopropionate (DMSP). Reisch CR, Moran MA, Whitman WB.	Dimethylsulfoniopropionate (DMSP) is a metabolite produced primarily by marine phytoplankton and is the main precursor to the climatically important gas dimethylsulfide (DMS). DMS is released upon bacterial catabolism of DMSP, but it is not the only possible fate of DMSP sulfur. An alternative demethylation/demethiolation pathway results in the eventual release of methanethiol, a highly reactive volatile sulfur compound that contributes little to the atmospheric sulfur flux. The activity of these pathways control the natural flux of sulfur released to the atmosphere. Although these biochemical pathways and the factors that regulate them are of great interest, they are poorly understood. Only recently have some of the genes and pathways responsible for DMSP catabolism been elucidated. Thus far, six different enzymes have been identified that catalyze the cleavage of DMSP, resulting in the release of DMS. In addition, five of these enzymes appear to produce acrylate, while one produces 3-hydroxypropionate. In contrast, only one enzyme, designated DmdA, has been identified that catalyzes the demethylation reaction producing methylmercaptopropionate (MMPA). The metabolism of MMPA is performed by a series of three coenzyme-A mediated reactions catalyzed by DmdB, DmdC, and DmdD. Interestingly, CandidatusPelagibacter ubique, a member of the SAR11 clade of Alphaproteobacteria that is highly abundant in marine surface waters, possessed functional DmdA, DmdB, and DmdC enzymes. Microbially mediated transformations of both DMS and methanethiol are also possible, although many of the biochemical and molecular genetic details are still unknown. This review will focus on the recent discoveries in the biochemical pathways that mineralize and assimilate DMSP carbon and sulfur, as well as the areas for which a comprehensive understanding is still lacking.	2011
4	23704947	Crystal structure of DmdD, a crotonase superfamily enzyme that catalyzes the hydration and hydrolysis of methylthioacryloyl-CoA. Tan D, Crabb WM, Whitman WB, Tong L.	Dimethyl-sulphoniopropionate (DMSP) is produced in abundance by marine phytoplankton, and the catabolism of this compound is an important source of carbon and reduced sulfur for marine bacteria and other organisms. The enzyme DmdD catalyzes the last step in the methanethiol (MeSH) pathway of DMSP catabolism. DmdD is a member of the crotonase superfamily of enzymes, and it catalyzes both the hydration and the hydrolysis of methylthioacryloyl-CoA (MTA-CoA), converting it to acetaldehyde, CO2, MeSH, and CoA. We report here the crystal structure of Ruegeria pomeroyi DmdD free enzyme at 1.5 Å resolution and the structures of the E121A mutant in complex with MTA-CoA and 3-methylmercaptopropionate-CoA (MMPA-CoA) at 1.8 Å resolution. DmdD is a hexamer, composed of a dimer of trimers where the three monomers of each trimer are related by a crystallographic 3-fold axis. The overall structure of this hexamer is similar to those of canonical crotonases. However, the C-terminal loops of DmdD in one of the trimers assume a different conformation and contribute to CoA binding in the active site of a neighboring monomer of the trimer, while these loops in the second trimer are disordered. MTA-CoA is bound deep in the active site in the first trimer, but shows a 1.5 Å shift in its position in the second trimer. MMPA-CoA has a similar binding mode to MTA-CoA in the first trimer. MMPA-CoA cannot be hydrated and is only hydrolyzed slowly by DmdD. Replacement of the sulfur atom in MMPA-CoA with a methylene group abolishes hydrolysis, suggesting that the unique property of the substrate is a major determinant of the hydrolysis activity of DmdD.	2013

Reisch C R , Stoudemayer M J , Varaljay V A , et al. Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria[J]. NATURE, 2011, 473(7346):208-211. Dazhi T , Crabb W M , Whitman W B , et al. Crystal Structure of DmdD, a Crotonase Superfamily Enzyme That Catalyzes the Hydration and Hydrolysis of Methylthioacryloyl-CoA[J]. PLoS ONE, 2013, 8(5):e63870-.