Biotransformation of cimetidine by Chlamydomonas sp. SI-16: CYP450-driven detoxification and immobilized photobioreactor validation.

Cimetidine (CIM), a widely prescribed histamine H2 receptor antagonist, is an emerging global contaminant owing to extensive clinical use and poor removal in conventional wastewater treatment. Herein, an indigenous microalgal strain Chlamydomonas sp. SI-16 with exceptional CIM tolerance was isolated from municipal wastewater, and its biotransformation potential was systematically investigated. The strain maintained robust degradation, with removal rates of 83.3%, 82.4%, and 82.1% at 1, 5, and 10 mg/L initial CIM concentrations, respectively. CIM exposure (10 mg/L) significantly upregulated algal antioxidant enzyme activities and extracellular polymeric substance secretion, activating cellular defense systems. Cytochrome P450 (CYP450) was identified as the key driver of CIM biotransformation, validated by enzymatic inhibition assays and stable molecular docking interactions. In real municipal wastewater, the algal system achieved 95.5% CIM removal within 24 days (vs. 66.0% for the non-inoculated control), with Caenorhabditis elegans assays confirming markedly reduced ecotoxicity of transformation products. A bio-rope immobilized photobioreactor also delivered 78.6% stable CIM removal, demonstrating engineering feasibility. As the first systematic report on CYP450-mediated CIM degradation and detoxification by environmental microalgae, these findings provide an engineering-feasible biocatalytic strategy for anti-ulcer pharmaceutical remediation in wastewater.