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含有素托的尼变种的合成和抗菌特异性

Chenhui Wang¹, Sanne Tervoort¹, Oscar P Kuipers¹

¹Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen 9747AG, The Netherlands.

ACS chemical biology

|September 12, 2025

概括

将化类类似物纳入抗菌 (RiPPs) 可以改变它们对特定细菌菌株的有效性. 这项研究成功合成了修改后的尼变体,证明了的化.

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:

核糖体产生的和翻译后修改的 (RiPPs) 是对抗多药耐药细菌的一类有前途的抗生素.
修改RiPPs,如尼,与化托残留物可能会提高抗微生物药物的有效性和特异性.
在RiPPs中加入化托类型的含量尚未得到充分研究.

研究的目的:

在 RiPP nisin A 位置1 生物合成纳入化托类型 (5-,5-,5--托) 使用托辅的 Lactococcus lactis 菌株.
评估由此产生的化尼变体对特定病原体的抗微生物活性和特异性.
探索素替代剂的化学特性与抗微生物生物活性之间的关系.

主要方法:

采用了托辅食菌株Lactococcus lactis菌株,用于改性尼的高效生物合成.
纳入了5-三聚 (5FW),5-三聚 (5CW),5-三聚 (5BW) 和5-甲基三聚 (5MW) 的尼A在位置1.
评估了野生型尼,I1W尼和基尼变体对四种不同的细菌病原体的抗菌活性.

主要成果:

在尼辛A中成功地将化托方类似物纳入尼辛A中.
野生类型和非基化I1W nisin表现出广泛的活性.
基尼变体显示了变化和菌株特异性的活性概况,观察到效率增加和减少.
在素特性 (电子负性,大小) 和抗菌活性之间没有明确的相关性,这表明复杂的菌株特异性机制.

结论:

类型的托芬类似物可以成功地被纳入生物活性RiPPs,使用辅助性L. lactis表达系统.
酸化是一种可行的策略,用于发现具有潜在定制病原体特异性的新型抗菌剂.
观察到的菌株特异性活性凸显了RiPP-病原体相互作用的复杂性,以及通过向修改微调抗菌性能的潜力.

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