Vital role of CYP450 in the biodegradation of antidiabetic drugs in the aerobic activated sludge system and the mechanisms

The extensive use of antidiabetic drugs (ADDs) and their detection in high concentrations in the environment have been extensively documented. However, the mechanism of ADDs dissipation in aquatic environments is still not well understood. This study thoroughly investigates the dissipation behavior of ADDs and the underlying mechanisms in the aerobic activated sludge system. The results indicate that the removal efficiencies of ADDs range from 3.98% to 100% within 48   h, largely due to the biodegradation process. Additionally, the gene expression of cytochrome P450 (CYP450) is shown to be significantly upregulated in most ADDs-polluted samples (P < 0.05), indicating the vital role of CYP450 enzymes in the biodegradation of ADDs. Enzyme inhibition experiments validated this hypothesis. Moreover, molecular docking and simulation results indicate that a strong correlation between the biodegradation of ADDs and the interactions between ADDs and CYP450 (E binding ). The differences in dissipation behavior among the tested ADDs are possibly due to their electrophilic characteristics. Overall, this study makes the initial contribution to a more profound comprehension of the crucial function of CYP450 enzymes in the dissipation behavior of ADDs in a typical aquatic environment. Environmental Implication This work underscores the role of CYP450 enzymes in the biodegradation of antidiabetic drugs (ADDs). While removal efficiencies vary widely, the biodegradation process can lead to the formation of degradation products potentially more toxic than the original compounds. This points to a critical need for advanced wastewater treatment technologies capable of addressing not only the removal of ADDs but also the mitigation of their toxic byproducts. The study's findings emphasize the importance of understanding the specific mechanisms of pharmaceutical pollution, which is essential for protecting aquatic ecosystems and, by extension, human health from the unintended consequences of widespread pharmaceutical use.