Molecular mechanisms of sulfadiazine biodegradation: The impact of intrinsic electric fields.

Sulfadiazine (SDZ), a kind of emerging contaminants, is highly enriched in the environment, posing serious risks to ecosystems and human health. Studies have shown that cytochrome P450 enzymes (CYPs) can degrade SDZ, but the detailed degradation mechanism remains unclear, and the degradation efficiency needs improvement. This study uses dynamic simulations, quantum mechanics/molecular mechanics methods and density functional theory to investigate the degradation mechanism and pathways of SDZ catalyzed by CYP120A1. The mechanisms involved in the hydrogen abstraction reaction are hydrogen atom transfer (HAT) and proton-coupled electron transfer (PCET), with the enzyme environment tend to inhibit the HAT reaction but promote the PCET reaction. Hydroxyl rebound and Smiles rearrangement are the rate-determining steps for the two mechanisms, respectively. Intrinsic electric field promotes hydroxyl rebound but interferes Smiles rearrangement. Residues THR258A and VAL318A are key amino acids in the reaction mechanism. This work aims to improve the degradation mechanism of emerging contaminants like sulfonamides, contributing to a better understanding of their environmental transformation process and providing theoretical support for developing green bioremediation technologies for emerging contaminants.