State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Lab for Marine Drugs and Byproducts of Pilot National Lab for Marine Science and Technology, Qingdao 266071, China; College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Lab for Marine Drugs and Byproducts of Pilot National Lab for Marine Science and Technology, Qingdao 266071, China; Key Laboratory of Sustainable Development of Polar Fisheries, Ministry of Agriculture and Rural Affairs, Qingdao 266071, China.
J Hazard Mater. 2024 Dec 5;480:136097. doi: 10.1016/j.jhazmat.2024.136097. Epub 2024 Oct 9.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widespread pollutants in aquatic environments, posing significant risks to both ecosystems and human health due to their persistence and bioaccumulation. Effective and sustainable degradation methods are urgently required to address this environmental challenge. This study aims to design and optimize a cytochrome P450BM3-based biocatalyst for the rapid and efficient degradation of NSAIDs by direct chemical intervention and protein engineering. The novel biocatalyst achieved efficient biodegradation of four common NSAIDs. Notably, the F87I/T268D mutant achieved 99.22 % degradation of diclofenac (DCF) within 10 min, and degraded meloxicam (MEL) and phenylbutazone (PBZ) at rates of 98.86 % and 90.51 % within 5 min, respectively. Furthermore, the F87G mutant accomplished 99.08 % degradation of acetaminophen (APAP) within just 2 min. The catalytic properties of P450BM3 and its mutants were evaluated through kinetic studies, and potential degradation pathways of the four NSAIDs were proposed in conjunction with UPLC-MS. This study provides a novel biocatalytic approach for the rapid degradation of NSAIDs in aquatic systems, offering considerable environmental benefits for pollution mitigation.
非甾体抗炎药（NSAIDs）是水生环境中广泛存在的污染物，由于其持久性和生物累积性，对生态系统和人类健康构成了重大风险。为了应对这一环境挑战，迫切需要有效的和可持续的降解方法。本研究旨在设计和优化基于细胞色素 P450BM3 的生物催化剂，通过直接化学干预和蛋白质工程实现 NSAIDs 的快速高效降解。新型生物催化剂实现了四种常见 NSAIDs 的有效生物降解。值得注意的是，F87I/T268D 突变体在 10 分钟内实现了 99.22%的双氯芬酸（DCF）降解，在 5 分钟内分别达到了 98.86%和 90.51%的美洛昔康（MEL）和苯并噻嗪（PBZ）降解速率。此外，F87G 突变体在短短 2 分钟内完成了 99.08%的对乙酰氨基酚（APAP）降解。通过动力学研究评估了 P450BM3 及其突变体的催化特性，并结合 UPLC-MS 提出了四种 NSAIDs 的潜在降解途径。本研究为水生系统中 NSAIDs 的快速降解提供了一种新的生物催化方法，为减轻污染提供了巨大的环境效益。
