近日，华南师范大学环境学院应光国教授团队刘有胜研究员、孙悦宏博士等人在国际知名期刊 《Chemical Engineering Journal》发表题为“Microbial biodegradation of abacavir: Isolation of Pseudomonas sp. A1 and elucidation of novel degradation pathways”的研究论文（DOI: 10.1016/j.cej.2025.166350）。首次从活性污泥中分离出高效降解抗病毒药物阿巴卡韦的功能菌株Pseudomonas sp. A1，该菌株在96小时内对1 mg/L阿巴卡韦的降解率达93.4%（半衰期28.27小时）。通过高分辨质谱鉴定15种转化产物，发现3种主要代谢物，并解析出两条由氧化/甲基化/开环等反应构成的新型降解途径。基于降解菌的全基因组测序和转录组学技术，揭示了氧化还原酶、转移酶及脱氢酶等编码基因显著上调，通过蛋白网络互作分析了驱动阿巴卡韦降解的潜在功能基因。毒性预测表明主要转化产物的急慢性毒性显著低于母体化合物，为水环境中药物污染物的生物修复提供新策略。
全文速览
针对阿巴卡韦去除不完全在环境中持久残留问题，本研究从活性污泥中分离出Pseudomonas sp. A1能在96小时内高效降解93.4%的1 mg/L阿巴卡韦（半衰期28.27小时），通过质谱鉴定出15种转化产物（包括主要代谢物TP-246、TP-260和TP-318），并揭示其通过两条新型途径（涉及氧化、甲基化、裂解、脱氨、加成、还原反应）实现降解。转录组分析显示氧化还原酶、转移酶及脱氢酶编码基因显著上调。ECOSAR预测结果表明主要代谢产物的毒性远低于母体化合物。
引言
抗病毒药物阿巴卡韦在全球拯救数百万HIV患者生命的同时，其环境残留已成隐患：常规污水处理厂仅能去除75-91%的污染物（残余浓度高达124 μg/L），导致河流、土壤及农作物广泛积累（番茄可富集达7.61 μg/kg），并可能通过食物链诱发心血管疾病风险。现有降解技术（如高级氧化）虽短期效率高，却依赖高能耗设备与极端条件；而微生物降解则主要是菌群研究。本研究通过分离高效降解单菌，解析降解分子机理，为废水中阿巴卡韦的污染控制提供可持续方案。
图文导读
富集高效降解菌群及其群落演化
Fig. 1. Enrichment of abacavir-degrading microorganisms and associated microbial diversity. (a) Removal efficiencies of five antiviral drugs by the enrichment system. (b) Degradation profile of abacavir across different enrichment generations. “A-2-2 mg/L” indicates the second enrichment generation initiated with 2 mg/L of abacavir, “A-3-4 mg/L” indicates the third generation at 4 mg/L; subsequent sample names follow the same naming convention. (c) Changes in microbial diversity during enrichment, represented by alpha diversity indices. “Origin” to “tenth” represents the enrichment system from the first generation to the tenth generation. A-2-1, A-2-2, and A-2-3 represent triplicate samples from the second enrichment generation, with subsequent samples named accordingly for each generation. (d) Principal coordinates analysis (PCoA) based on the ASV level showing differences in microbial community composition differences during enrichment (R = 0.8569, P = 0.001). (e) Bar plot illustrating the changes in the microbial community structure throughout the enrichment process.
以活性污泥为接种源构建富集系统，阿巴卡韦在1 mg/L浓度下12小时完全降解。经多代富集逐步增加初始浓度至4 mg/L，第十代降解效率显著提高，132小时阿巴卡韦残留浓度降至17.2%。群落多样性（Ace指数）随富集进程递减并趋于稳定，功能菌群结构重构：亚硝化单胞菌属丰度显著提升（响应无机盐培养基铵源），协同黄杆菌科共代谢强化降解。假单胞菌虽为低丰度菌群，经分离确证为核心降解菌，印证低丰度关键类群生态理论。主坐标分析（PCoA）显示第八至十代群落高度收敛，成功驯化适合用于分离单菌的菌群。
阿巴卡韦降解菌的分离、鉴定与表征
Fig. 2. Screening and characterization of abacavir-degrading bacteria. (a) Degradation efficiency of 10 isolated bacterial strains at an initial abacavir concentration of 1 mg/L. (b) Degradation efficiency of strains abacavir-1 (A1) and abacavir-2 (A2) at an initial abacavir concentration of 1 mg/L. (c) Colony morphology of strain A1 on an LB agar plate after 24 hours of streak culturing. (d) Scanning electron microscopy (SEM) image of strain A1 (magnification = 40,000×, electron high tension = 2.00 kV, working distance = 5.7 mm, signal A = SE2).
最终富集菌落平板分离获得10株降解菌，其中九株为假单胞菌A1，224小时达64.0-80.0%，显著优于芽孢杆菌A2株（224小时仅24.6%）。A1菌落为不透明湿润圆形（图2c），电镜显示短杆状细胞（1.5–2.5 μm×0.5 μm）。全基因组系统发育分析：A1与knackmussii和delhiensis同源性达99.41%/99.22%。
阿巴卡韦降解路径与产物
Fig. 3. Biodegradation of 1 mg/L abacavir by strain A1. (a) First-order kinetic fitting for abacavir degradation by A1. (b) Identified transformation products formed during the degradation process. (c) Proposed biodegradation pathways of abacavir. Brown arrows indicate transformation products exclusively generated in the A1-treated group, while green arrows represent products detected in both the sterile control group and the experimental group, with significantly higher abundance in the experimental group.
对数期A1菌株96小时降解93.4%阿巴卡韦（半衰期28.27小时），降解效率显著。HRMS鉴定15种转化产物，TP-246/TP-318（早期高累积）与TP-260（TP-246甲基化次生）占响应值主体；ECOSAR预测（Fig. S7）显示关键产物急性毒性（鱼LC50：TP-318达3149.75 mg/L vs 母药36.62 mg/L）与慢性毒性（鱼ChV：TP-318达10.26 mg/L vs 母药0.30 mg/L）显著降低，多数转化产物LC50/EC50 > 100 mg/L、ChV > 10 mg/L，证实降解路径有效降低生态风险。
阿巴卡韦降解过程中A1菌株的潜在降解机制
Fig. 4. Transcriptomic analysis of Pseudomonas sp. A1 during abacavir degradation. A_1_0-h and the positive control group A_1_con_96-h were used as the control and experimental groups, respectively, for comparative analysis. (a) Statistical analysis of gene expression differences at different time points. (b) GO enrichment analysis of upregulated mRNAs at 24 hours compared to 0 hours. The x-axis represents GO terms, while bar height reflects significance. The left y-axis shows -log10(Padjust), and the right y-axis represents the number of genes involved. Red points indicate the number of genes associated with each GO term. The top 10 enriched results GO categories are displayed under Padjust < 0.05. (c) Network analysis of the identified key metabolic genes based on their protein-protein interaction values. Larger circles indicate stronger interaction.
转录组分析揭示A1菌株降解早期（24-48小时）显著上调氧化还原酶基因（175个，主导母环氧化形成TP-246/TP-318）与转运蛋白基因（108-119个），驱动快速降解（48小时去除率64.3%）；蛋白互作网络分析显示algA, arnA, paaH, prmB, guaA, iaaH，and cysI为潜在功能酶，共同形成多酶联动的代谢机制。
小结
本研究首次分离假单胞菌A1并阐明其通过转移酶/脱氢酶等关键酶高效降解阿巴卡韦的潜在分子机制（半衰期28.27 h），形成如TP-246/TP-318/TP-260等低毒产物，为微生物法治理药物污染提供了新路径。未来需重点解决复杂废水环境中菌株-微生物群落互作及降解稳定性难题，通过代谢工程优化与技术整合推进工程化应用。
全文链接
Yuehong Sun, Jinna Zhang, Yuanyuan Zhang, Hengyu Wu, Fengqi Xie, Jiaru Ma, Yousheng Liu, Guangguo Ying, Microbial biodegradation of abacavir: Isolation of Pseudomonas sp. A1 and elucidation of novel degradation pathways, Chemical Engineering Journal. 2025. 521, 166350.