在硫生物合成过程中的酶性胺芳香化
Andrew J Rice1,2, Jarrett M Pelton3, Nicholas J Kramer3
1Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|November 9, 2022
概括
研究人员阐明了含有 thiazole 的 pyritides (thiopeptides) 中 pyridine 的形成机制. 确定了关键的氨酸残留物,促进了这个复杂的生物合成途径的最终芳香化步骤.
科学领域:
- 生物化学
- 分子生物学
- 自然产品合成
背景情况:
- 含有 thiazole 的 pyritides 或 thiopeptides 是复杂的核糖体合成和翻译后修饰的 (RiPPs) 已知具有强大的生物活性.
- 一个关键的结构特征是通过酶 [4 + 2] 循环添加形成的二环,尽管其形成机制尚不清楚.
研究的目的:
- 为了研究蛋白生物合成中蛋白环形成的不太了解的机制.
- 确定酶性胺合成途径中的关键残留物和步骤.
主要方法:
- 使用向突变和动力测试来研究硫胺合成酶.
- 采用基质类似物,酶基质交叉链接和化学救援实验.
- 在Bycroft-Gowland中间体的识别基础上构建.
主要成果:
- 描述了几种保存残留物在硫胺合成中的作用.
- 鉴定出一个关键的氨酸残留物, 对于氨酸形成的最终芳香化阶段至关重要.
- 提供了对 [4 + 2] 循环添加和随后的氨酸合成的机制见解.
结论:
- 建立了胺形成的机制框架.
- 突出了特定的氨酸在芳香化过程中的关键作用.
- 奠定了未来生物合成和工程研究的基础.
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