Zheng_2024_Environ.Sci.Technol__

Commercial herbicides, particularly sulfonylureas, are used worldwide and pose a significant challenge to environmental sustainability. The efficient degradation of sulfonylurea herbicides is critical. SulE, an esterase isolated from the bacterial strain Hansschlegelia zhihuaiae S113, shows degradation activity toward sulfonylurea herbicides. However, the detailed catalytic mechanism remains vague to a large extent. Herein, we decipher the SulE(P44R)-catalyzed degradation mechanism of sulfonylurea herbicides using hybrid quantum mechanics and molecular mechanics approaches. Our results show that the degradation of sulfonylureas catalyzed by SulE(P44R) involves four concerted elementary steps. The rate-determining step has an energy barrier range of 19.7-21.4 kcal.mol(-1), consistent with the experimentally determined range of 16.0-18.0 kcal.mol(-1). Distortion/interaction analysis demonstrates that active-site amino acids play a vital role in the enzymatic catalytic efficacy. The unique architecture of SulE(P44R)'s active site can serve as an excellent template for designing artificial catalysts. Key structural and charge parameters affecting catalytic activity were systematically screened and identified. Based on the elucidated degradation mechanism, several new herbicides with both high herbicidal activity and biodegradability were developed with the aid of a high-throughput strategy. Our findings may advance the application of sulfonylurea herbicides within the framework of environmental sustainability.