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结构指导工程的一种乱伦的O-甲基转移酶的SAM再生生物催化平台的甲基化药品的结构指导工程

Xiran Xiong¹, Jun Song^1,2, Shihan Li¹

¹School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|December 19, 2025

概括

研究人员设计了一种多功能植物酶,用于高效的甲基化,为生产抗炎药物创造了一个可持续的平台. 这种生物催化剂克服了昂贵的S-adenosyl-L-methionine (SAM) 的局限性,并使克尺度合成成为可能.

科学领域:

生物催化剂是一种生物催化剂.
酵素工程是什么意思酵素工程
自然产品的合成自然产品的合成

背景情况:

植物O-甲基转移酶对于药物设计和天然产品生物合成至关重要.
它们的应用受到基质特异性和依赖昂贵的S-adenosyl-L-methionine (SAM) 的限制.

研究的目的:

识别和表征一种来自Selaginella moellendorffii的新型O-甲基转移酶 (SmOMT),其特性得到了改进.
开发一个高效的酶甲基化系统与SAM再生,以实现可持续的合成.

主要方法:

识别和描述SmOMT,包括结构和分子动力学研究.
酶工程是为了制造具有增强活性的双重突变 (SmOMT^M2).
用化物甲基转移酶 (AtHMT^V140T) 构建一个级联系统,用于SAM再生.
使用iMARS平台设计一个聚变酶 (AtHMT^V140T-L_{95-SmOMT^M2) 的设计.}

主要成果:

SmOMT表现出基质乱交,区域选择性和N-甲基化活性.
SmOMT^M2显示了增强的催化效率.
工程级联系统和聚变酶使SAM能够高效地再生.
实现了具有增强抗炎活性的甲基化化合物的グラム级合成.

结论:

开发了一种多功能甲基化生物催化剂 (SmOMT^M2).
建立了一个高效的SAM再生甲基化平台,克服了以前的局限性.
这项工作使高价值甲基化药品的可持续生产成为可能.

关键词:

在SAM的再生过程中,SAM的再生聚变酶是一种聚变酶.植物的O-甲基转移酶.结构的结构结构的结构.基质的杂乱性基质的杂乱性

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