异功能但结构上不同的甲基转移酶用于迪提奥皮罗龙的多样化
Li Su, Eva M Huber1, Margaretha Westphalen2
1Technical University of Munich, TUM School of Natural Sciences, Department of Bioscience, Center for Protein Assemblies, 85748, Garching, Germany.
Angewandte Chemie (International ed. in English)
|August 26, 2024
概括
研究人员确定了XrdM酶,该酶负责细菌中甲基化纳丁 (XRD). 这一发现揭示了dithiolopyrrolone (DTP) 生物合成,并揭示了融合酶的进化.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 迪提奥皮罗隆 (DTP) 天然产品具有显著的抗菌,抗真菌和抗癌特性.
- 对于微调生物活性而言,DTP核心的胺N-甲基化是至关重要的,但负责的酶往往没有特征.
- 谢诺哈布丁 (XRD) 是一种DTP天然产品,具有潜在的治疗应用.
研究的目的:
- 确定负责Xenorhabdus doucetiae中的Xenorhabdin (XRD) 胺基N-甲基化酶.
- 研究XrdM与其他DTP相关的甲基转移酶之间的结构和功能关系.
- 扩大对DTP生物合成中的非核糖体后合成酶 (NRPS) 胺基甲基化的理解.
主要方法:
- 基因鉴定和XrdM甲基转移酶的特征.
- 进行X射线晶体学以确定酶结构.
- 酶活性测定和位点定向突变发生,以探测功能.
- 生物信息分析和比较建模.
主要成果:
- 胺基甲基转移酶XrdM被确定为负责Xenorhabdus doucetiae中的Xenorhabdin (XRD) 甲基化.
- 在功能上,XrdM与DtpM (参与硫素生物合成) 类似,但具有与X射线无关的X射线结构.
- 这项研究揭示了两个结构上不同的酶的融合进化,它们催化了相同的甲基化反应.
结论:
- XrdM是一种参与DTP生物合成的新型酶,扩展了已知的NRPS后修饰机制.
- 这些发现突显了酶功能的融合进化,相同的生物化学反应具有不同的结构解决方案.
- 这项研究提供了对自然产品生物合成和酶进化的多样性的见解.
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