在形态基因兰西 SapT 中意外的甲基兰西立体化学
Raymond Sarksian1, Julian D Hegemann2, Max A Simon3
1Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61822, United States.
Journal of the American Chemical Society
|March 30, 2022
概括
研究人员在兰氏中发现了甲基氨酸 (MeLan) 残留物中的新立体化学,这是一种通过核糖体合成和翻译后修改的类. 这一发现扩大了我们对兰氏结构和生物活性的理解.
科学领域:
- 生物化学
- 分子生物学
- 微生物学
背景情况:
- 兰氏是一种含有兰氏 (Lan) 或甲基兰氏 (MeLan) 交叉链的核糖体合成和转化后修饰 (RiPP).
- (Me) 兰残留物的立体化学对于兰氏的生物活性至关重要.
- 之前描述的兰氏在其MeLan残留物中仅表现出2S,3S或2R,3R立体化学.
研究的目的:
- 在大肠杆菌中复制I类 lanthipeptide SapT的生物合成途径.
- 在异质生成的SapT中描述MeLan残留的立体化学.
- 调查MeLan新型立体化学在其他兰氏中的潜在流行和起源.
主要方法:
- 在大肠杆菌中SapT生物合成途径的异构表达.
- 用于立体化学分析的化学标准的合成.
- 兰氏生物合成酶的生物信息分析.
- 检测反应机制的位点定向突变发生.
主要成果:
- 在大肠杆菌中成功重建了SapT生物合成途径.
- 通过2S,3R立体化学 (d-allo-l-MeLan) 在SapT中确定了三种MeLan残留物,这是兰氏的新发现.
- 在Streptomyces coelicolor中进行的生物信息分析和实验验证证了d- allo- l- MeLan在其他兰氏中的存在.
- 提出并提供解释这种独特立体化学的机制的证据.
结论:
- 在SapT中发现d-allo-l-MeLan扩大了已知的兰氏的立体化学多样性.
- 生物信息学和实验数据表明这种立体化学不仅仅存在于SapT中,也可能存在于其他兰氏中.
- 这项研究提供了关于MeLan形成和兰氏生物合成的酶机制的见解.
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