一在体外对宏循环脱酸的核糖体合成
Masanobu Nagano1, Yichao Huang1, Richard Obexer1
1Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|March 18, 2021
概括
研究人员使用一种新型的Ser-Pro-Cys-Gly (SPCG) 基因开发了一种单式核糖体合成. 这种方法有效地创建多种CDP库,用于发现新的生物活性化合物.
科学领域:
- 生物化学
- 合成生物学
- 医学化学
背景情况:
- 宏循环除 (CDP) 是一种具有多种生物活性的重要自然产品.
- 传统的CDP合成通常很复杂,产量也很低.
- 核糖体合成为有效的和脱生产提供了一个有前途的途径.
研究的目的:
- 开发一种新的,单一的方法,用于对宏循环的核糖体合成.
- 确定和描述一个能够有效形成CDP的关键基因.
- 展示该方法用于生成多种CDP库的多功能性.
主要方法:
- 在实验室中选择用于识别具有自化活性的Ser-Pro-Cys-Gly (SPCG) 基因.
- 含有SPCG基因的线性和一个酸捐赠体被通过核糖体合成.
- 在循环化过程中采用了S-O内分子转移.
- 对SPCG基因进行突变分析以了解结构-活性关系.
主要成果:
- 发现了一种新型的SPCG基因,促进了高效的自我化和分子内S-O转移.
- 实现了高效率的循环脱胺 (CDP) 单核糖体合成,主要独立于环形大小和序列.
- 突变分析表明SXCX残留组合对转移效率的关键作用.
- 该方法已成功应用于合成具有不同环形大小和序列的宏环.
结论:
- 已经建立了一个简单有效的单核糖体合成方法.
- 发现的SPCG基因是通过核糖体合成自发形成循环脱的关键.
- 这种方法为构建多种CDP库提供了强大的平台,加速了新生物活性化合物的发现.
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