Reaction mechanism of the PuDddK dimethylsulfoniopropionate lyase and cofactor effects of various transition metal ions

Abstract

The microbial cleavage of dimethylsulfoniopropionate (DMSP) produces volatile dimethyl sulfide (DMS) via the lyase pathway, playing a crucial role in the global sulfur cycle. Herein, the DMSP decomposition catalyzed by PuDddK (a DMSP lyase) devised with various transition metal ion cofactors are investigated using density functional calculations. The PuDddK 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_β–S bond cleavage and C_α = C_β double bond formation. The PuDddK enzymes with diverse divalent metal ions (Ni²⁺, Mn²⁺, Fe²⁺, Co²⁺, Zn²⁺, and Cu²⁺) incorporated prefer DMSP as a monodentate ligand. The cases of Ni²⁺, Mn²⁺, Fe²⁺, Co²⁺, and Zn²⁺ 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 Cu²⁺, 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 Fe³⁺-dependent PuDddK is derived from an electron transfer from the Tyr64 phenolate to Fe³⁺, with the implication that the PuDddK activity may be primarily affected by the redox effects induced by a strongly oxidizing transition metal ion (like Fe³⁺).