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伪氨基酸合成酶的理性工程使得可以获得3糖,并抑制细菌病原体的运动性

James M Jeffries¹, Abigail J Walklett¹, Natasha E Hatton¹

¹York Structural Biology Lab, Department of Chemistry, University of York, York, YO10 5DD, UK.

Angewandte Chemie (International ed. in English)

|October 24, 2025

概括

研究人员设计了一种关键酶,以制造一种新的化糖,3-化伪氨基酸. 这一突破为抑制细菌糖化和通过减少病原体运动来打击抗菌素耐药性提供了新的策略.

科学领域:

生物化学生物化学
微生物学微生物学
合成生物学合成生物学

背景情况:

伪氨基酸是细菌O-糖化过程中必不可少的糖,对病原体的运动性和毒性至关重要.
坎比洛巴克特 (Campylobacter jejuni) 依赖伪氨基酸进行鞭毛蛋白糖化,影响其感染宿主的能力.

研究的目的:

设计伪氨基酸合成酶 (PseI),用于新型化伪氨基酸的合成.
研究这些化糖作为细菌糖化和运动的抑制剂的潜力.

主要方法:

合理工程PseI活跃站点,以提高与非自然基质的周转.
化学酶合成的3-化伪氨基酸 (3-(eq) -F-Pse5Ac7Ac).
评估3-(eq) -F-Pse5Ac7Ac对Campylobacter jejuni运动性及其由细菌酶的代谢处理的影响.

主要成果:

通过PseI的成功工程,使得3-(eq) -F-Pse5Ac7Ac的可扩展合成成为可能.
用3-(eq) -F-Pse5Ac7Ac对C. jejuni的治疗显著降低了细菌的运动性.
细菌酶 (PseF) 将化糖加工成其CMP供体形式,即CMP-3-(eq) -F-Pse5Ac7Ac.

结论:

化伪氨基酸可以有效地降低细菌的运动性,显示出一种新的抗病毒性机制.
这项研究确立了一个潜在的新型代谢抑制剂类别,针对细菌糖化.
这些发现为抗病原细菌的抗运动策略铺平了道路,为传统抗生素提供了替代品,并解决了抗菌素耐药性的问题.

关键词:

细菌抗摩提林的抗菌剂.化学酶合成的合成方法化糖是含有的糖类之一.非氨酸酸的非氨酸酸.伪氨基酸是一种伪氨基酸.有理性的突变发生.-基托酸糖类 -基托酸糖类

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