一个集成模块在抗生素mupirocin的生物合成中执行选择性的"在线"氧化
Ashley J Winter1, Felix de Courcy-Ireland1, Annabel P Phillips1
1School of Chemistry, University of Bristol, BS8 1TS, Bristol, UK.
Angewandte Chemie (International ed. in English)
|August 6, 2024
概括
研究人员通过识别MmpE来阐明抗生素mupirocin的生物合成.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 有机化学 有机化学
背景情况:
- 穆皮罗辛是一种由Pseudomonas fluorescens产生的强效抗生素,具有复杂的生物合成过程,涉及伪蒙酸 (PA).
- 在PA生物合成中的关键步骤,包括环氧化和四基 (THP) 环形成,在机理上仍然不清楚.
- 了解这些步骤对于阐明完整的mupirocin生物合成途径至关重要.
研究的目的:
- 研究mupirocin生物合成中的环氧化机制和时间.
- 为了确定参与初始环氧化步骤的特定酶和基质.
- 为了澄清环氧化模块在聚乙合成酶 (PKS) 组装线中的整合.
主要方法:
- 采用纯化的MmpE氧化还原酶域和MmpE_ACP的体外生化试验.
- 一个有六个不对称中心的线性多基基片段的合成.
- 用Pseudomonas fluorescens进行养研究NCIMB 10586.6.
主要成果:
- 证明MmpE迷你模块在与乙载体蛋白 (ACP) 结合的基质上进行"in-cis"环氧化.
- 确定了一家以前未被注释的参与基质道化的ACP (MmpE_ACP).
- 通过体外和养研究证实了这种选择性环氧化过程的时间和链长度依赖性.
结论:
- MmpE模块负责mupirocin生物合成中的关键早期环氧化步骤.
- 这种环氧化发生在"线上"的ACP-bound中间体上,THP环形形成之前.
- 对这一步骤的机械洞察力为PA-B生成提供了更清晰的理解.
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