State Environmental Protection Key Laboratory of Microorganism Application and Risk Control, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
School of Environment, Tsinghua University, Beijing, China.
Microbiome. 2022 Oct 24;10(1):180. doi: 10.1186/s40168-022-01361-5.
As a widely used broad-spectrum antibiotic, chloramphenicol is prone to be released into environments, thus resulting in the disturbance of ecosystem stability as well as the emergence of antibiotic resistance genes. Microbes play a vital role in the decomposition of chloramphenicol in the environment, and the biotransformation processes are especially dependent on synergistic interactions and metabolite exchanges among microbes. Herein, the comprehensive chloramphenicol biotransformation pathway, key metabolic enzymes, and interspecies interactions in an activated sludge-enriched consortium were elucidated using integrated multi-omics and cultivation-based approaches.
The initial biotransformation steps were the oxidization at the C-OH and C-OH groups, the isomerization at C, and the acetylation at C-OH of chloramphenicol. Among them, the isomerization is an entirely new biotransformation pathway of chloramphenicol discovered for the first time. Furthermore, we identified a novel glucose-methanol-choline oxidoreductase responsible for the oxidization of the C-OH group in Sphingomonas sp. and Caballeronia sp. Moreover, the subsequent biotransformation steps, corresponding catalyzing enzymes, and the microbial players responsible for each step were deciphered. Synergistic interactions between Sphingomonas sp. and Caballeronia sp. or Cupriavidus sp. significantly promoted chloramphenicol mineralization, and the substrate exchange interaction network occurred actively among key microbes.
This study provides desirable strain and enzyme resources for enhanced bioremediation of chloramphenicol-contaminated hotspot sites such as pharmaceutical wastewater and livestock and poultry wastewater. The in-depth understanding of the chloramphenicol biotransformation mechanisms and microbial interactions will not only guide the bioremediation of organic pollutants but also provide valuable knowledge for environmental microbiology and biotechnological exploitation. Video Abstract.
氯霉素作为一种广泛使用的广谱抗生素，容易释放到环境中，从而破坏生态系统稳定性并产生抗生素耐药基因。微生物在环境中氯霉素的分解中起着至关重要的作用，其生物转化过程尤其依赖于微生物之间的协同相互作用和代谢物交换。本文采用综合多组学和基于培养的方法，阐明了富含有机物污泥中氯霉素的综合生物转化途径、关键代谢酶和种间相互作用。
氯霉素的初始生物转化步骤为 C-OH 和 C-OH 基团的氧化、C 位的异构化以及 C-OH 位的乙酰化。其中，异构化是首次发现的氯霉素的全新生物转化途径。此外，我们鉴定了一种新型葡萄糖-甲醇-胆碱氧化还原酶，负责氧化单胞菌属和 Caballeronia 属中 C-OH 基团。此外，还解析了随后的生物转化步骤、对应的催化酶以及负责每个步骤的微生物。单胞菌属和 Caballeronia 属或贪铜菌属之间的协同相互作用显著促进了氯霉素的矿化，关键微生物之间发生了活跃的底物交换相互作用网络。
本研究为增强制药废水和禽畜废水等氯霉素污染热点区域的生物修复提供了理想的菌株和酶资源。深入了解氯霉素的生物转化机制和微生物相互作用不仅将指导有机污染物的生物修复，还将为环境微生物学和生物技术开发提供有价值的知识。视频摘要。
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