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前体指导的生物合成和生物活性的三白Cpip,一个新的三白C类比含有pipecolic酸

Hideki Hashizume¹, Ryuichi Sawa², Yumiko Kubota²

¹Laboratory of Microbiology, Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan. hashizumeh@bikaken.or.jp.

The Journal of antibiotics

|January 24, 2024

概括

三烯C中的L-prolyl-D-proline结构对其强大的抗菌活性至关重要,这种抗菌活性对抗了耐甲林耐药性黄金葡萄球菌等细菌. 取而代之的普罗林与pipecolic 酸削弱了它的有效性.

科学领域:

微生物学微生物学
药用化学医学化学
生物化学生化学

背景情况:

三烯C是一种循环脂,对抗抗甲素耐药黄金葡萄球菌 (MRSA) 有强烈的疗效.
三烯含有L-prolyl-D-proline基结构,已知可以诱导中的毛结构.
这种基结构对抗菌活性的贡献以前是未知的.

研究的目的:

调查L-prolyl-D-proline基结构在三烯酸C的抗菌活性中的作用.
为了合成和表征用修饰的氨酸残留物合成和表征trippropeptin类似物.

主要方法:

使用前体指导生物合成,用pipecolic酸替换trippropeptin C中的proline残留物.
分离和净化由此产生的三白类似物,三白Cpip.
在体外对抗微生物敏感性测试,对包括MRSA在内的格拉姆阳性细菌进行检测.

主要成果:

含有一种L-pipecolic酸而不是L-proline的Tripropeptin Cpip,已成功合成.
三烯Cpip表现出降低的抗菌活性,比三烯C弱两到四倍.
对标准和耐药的格拉姆阳性细菌菌株均观察到活性下降.

结论:

L-prolyl-D-proline基结构对于trippropeptin C的高强度至关重要.
对这种特定基结构的修改会显著影响抗菌疗效.
这些发现提供了关于三烯的结构-活性关系的见解,指导未来的抗生素开发.

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