Reaction mechanism of the Pu DddK dimethylsulfoniopropionate lyase and cofactor effects of various transition metal ions.

The microbial cleavage of dimethylsulfoniopropionate (DMSP) produces volatile dimethyl sulfide (DMS) the lyase pathway, playing a crucial role in the global sulfur cycle. Herein, the DMSP decomposition catalyzed by DddK (a DMSP lyase) devised with various transition metal ion cofactors are investigated using density functional calculations. The DddK reaction has been demonstrated to employ a concerted β-elimination mechanism, where the substrate α-proton abstraction by the deprotonated Tyr64 occurs simultaneously with the C-S bond cleavage and C = C double bond formation. The DddK enzymes with diverse divalent metal ions (Ni, Mn, Fe, Co, Zn, and Cu) incorporated prefer DMSP as a monodentate ligand. The cases of Ni, Mn, Fe, Co, and Zn with the same 3His-1Glu ligands have close reaction energy barriers, indicating that the lyase activity may be hardly affected by the divalent transition metal type with the same ligand type and number. The coordination loss of one histidine in Cu, forming a 2His-1Glu architecture, leads to a lower activity, revealing that the 3His-1Glu ligand set used by DddK appears to be a scaffold capable of more efficiently catalyzing the DMSP decomposition. Further analysis reveals that the inactivation of Fe-dependent DddK is derived from an electron transfer from the Tyr64 phenolate to Fe, with the implication that the DddK activity may be primarily affected by the redox effects induced by a strongly oxidizing transition metal ion (like Fe).