<br>废水中胞外肽酶水解抗菌肽,Environmental Science & Technology

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废水中胞外肽酶水解抗菌肽
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-12-16 , DOI: 10.1021/acs.est.3c06506
Natalie Wichmann _{1,

2} , Richard Gruseck ₁ , Michael Zumstein ₁

Affiliation

几种抗菌肽（AMP）正在成为有前景的新型抗生素。当使用后释放到废水流中时，AMP 可能会被废水肽酶水解并失活，从而减少释放到废水接收环境中的活性抗菌剂。更好地了解废水系统中 AMP 命运的关键一步是研究废水肽酶的活性和特异性。在这里，我们量化了整个废水处理过程中不同阶段的细胞外提取物中的肽酶活性。对于所有四个测试的城市污水处理厂，我们检测到原废水中的活性最高。作为补充，我们评估了原废水提取物中酶对 10 种选定 AMP 进行生物转化的潜力。我们发现 AMP 对酶促转化的敏感性存在很大差异，表明提取的酶具有显着的底物特异性。为了深入了解肽酶的特异性，我们搜索了快速生物转化的 AMP 的水解产物，并使用合成标准对选定的产物进行了定量。我们发现水解发生在特定位点，并且这些位点在四种测试废水中显着保留。总之，这些发现提供了对废水系统中 AMP 命运的深入了解，并可为可被废水肽酶水解的肽类抗生素的选择和设计提供信息。

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Hydrolysis of Antimicrobial Peptides by Extracellular Peptidases in Wastewater

Several antimicrobial peptides (AMPs) are emerging as promising novel antibiotics. When released into wastewater streams after use, AMPs might be hydrolyzed and inactivated by wastewater peptidases─resulting in a reduced release of active antimicrobials into wastewater-receiving environments. A key step towards a better understanding of the fate of AMPs in wastewater systems is to investigate the activity and specificity of wastewater peptidases. Here, we quantified peptidase activity in extracellular extracts from different stages throughout the wastewater treatment process. For all four tested municipal wastewater treatment plants, we detected highest activity in raw wastewater. Complementarily, we assessed the potential of enzymes in raw wastewater extracts to biotransform 10 selected AMPs. We found large variations in the susceptibility of AMPs to enzymatic transformation, indicating substantial substrate specificity of extracted enzymes. To obtain insights into peptidase specificities, we searched for hydrolysis products of rapidly biotransformed AMPs and quantified selected products using synthetic standards. We found that hydrolysis occurred at specific sites and that these sites were remarkably conserved across the four tested wastewaters. Together, these findings provide insights into the fate of AMPs in wastewater systems and can inform the selection and design of peptide-based antibiotics that are hydrolyzable by wastewater peptidases.

更新日期：2023-12-16

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