Enzymatic Degradation\ntoward Herbicides: The Case\nof the Sulfonylureas

Commercial herbicides, particularly sulfonylureas, are\nused worldwide\nand pose a significant challenge to environmental sustainability.\nThe efficient degradation of sulfonylurea herbicides is critical.\nSulE, an esterase isolated from the bacterial strain Hansschlegelia zhihuaiae S113, shows degradation\nactivity toward sulfonylurea herbicides. However, the detailed catalytic\nmechanism remains vague to a large extent. Herein, we decipher the\nSulE<sup>P44R</sup>-catalyzed degradation mechanism of sulfonylurea\nherbicides using hybrid quantum mechanics and molecular mechanics\napproaches. Our results show that the degradation of sulfonylureas\ncatalyzed by SulE<sup>P44R</sup> involves four concerted elementary\nsteps. The rate-determining step has an energy barrier range of 19.7–21.4\nkcal·mol<sup>–1</sup>, consistent with the experimentally\ndetermined range of 16.0–18.0 kcal·mol<sup>–1</sup>. Distortion/interaction analysis demonstrates that active-site amino\nacids play a vital role in the enzymatic catalytic efficacy. The unique\narchitecture of SulE<sup>P44R</sup>’s active site can serve\nas an excellent template for designing artificial catalysts. Key structural\nand charge parameters affecting catalytic activity were systematically\nscreened and identified. Based on the elucidated degradation mechanism,\nseveral new herbicides with both high herbicidal activity and biodegradability\nwere developed with the aid of a high-throughput strategy. Our findings\nmay advance the application of sulfonylurea herbicides within the\nframework of environmental sustainability.