穆皮洛辛多基酸合成酶α-氧化双模块的结构和功能
Ashley J Winter1, R Nisha Khanizeman1, Abigail M C Barker-Mountford1
1School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.
Angewandte Chemie (International ed. in English)
|September 28, 2023
概括
研究人员在mupirocin生物合成中表征了α-氧化双模块. 这项研究揭示了MupA酶对抗生素生产至关重要的时间,基质特异性和乙载体蛋白 (ACP) 的依赖性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 微生物学 微生物学
背景情况:
- 穆皮罗辛是一种重要的抗生素,由*伪菌光体*中的一种跨AT型I多基酸合成酶 (PKS) 合成.
- 关键的代谢物,伪蒙酸A (PA-A),具有一个四基 (THP) 核心与一个6-基团.
- 假设这种基团是通过基载体蛋白 (ACP) 结合的多基基链的α-基化引入的.
研究的目的:
- 描述mupirocin生物合成途径中的α-基化双模块.
- 为了阐明酶的机制,基质的特异性,以及氧化过程的时间.
- 调查ACP的作用和MupA在PKS组装线上的相互作用.
主要方法:
- 一种 in vitro 方法,结合了纯化的酶成分.
- 化学合成,同位素标记,质谱和NMR光谱学.
- 在体内研究,以补充体外发现.
主要成果:
- 穆皮洛辛途径的α-基化双模块的第一个特征.
- 揭示了MupA的基化精确时间,其基质特异性和ACP依赖性.
- MmpA KS0表现出放松的基质特异性,表明对MupA招募的时空控制.
- 检测到多个模块间的MupA/ACP相互作用,表明它们与PKS组合集成.
结论:
- 这项研究提供了对MupA介导的mupirocin生物合成中的α-基化步骤的全面了解.
- 这些发现凸显了酶组件和PKS机制之间的复杂协调.
- 特征的α-基化双模块对于正确组装伪蒙酸A是必不可少的.
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