一种7个跨膜甲基转移酶,催化了性多糖胺单氧基酶的N终端基化
Tanveer S Batth1, Jonas L Simonsen2,3, Cristina Hernández-Rollán4
1The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen Denmark, Copenhagen, Denmark. t.batth@cpr.ku.dk.
Nature communications
|July 14, 2023
概括
研究人员发现了一种新型酶,N-终端胺甲基转移酶 (NHMT),它负责在酸多糖胺单氧化酶 (LPMOs) 中甲基化关键胺残留物. 这一发现增强了对LPMO稳定性的理解,并为酶修饰提供了生物技术应用.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 工业生物技术 工业生物技术
背景情况:
- 性多糖化单氧化酶 (LPMOs) 是关键的氧化酶,用于降解纤维素,对于生物质利用至关重要.
- 在LPMOs中,N终端的histidine (His1) 需要甲基化以防止自身氧化失活,这是由未知的甲基转移酶介导的过程.
- 丝状真菌使用这种甲基化来增强LPMO的稳定性和功能.
研究的目的:
- 为了确定特定的甲基转移酶酶,负责在LPMOs中对N-终端胺 (His1) 的翻译后修饰.
- 描述已识别的酶,并探索其用于蛋白质修饰的生物技术潜力.
主要方法:
- 利用基于质谱的定量蛋白质组学.
- 在Aspergillus nidulans中进行了系统的CRISPR/Cas9淘汰查.
- 进行了有针对性的蛋白质组学和同局部化研究.
- 在Komagataella phaffii.研究的重组表达.
主要成果:
- 鉴定了由基因AN4663编码的N终端胺甲基转移酶 (NHMT) 作为LPMOs中His1甲基化唯一负责的酶.
- NHMT具有独特的结构,具有七个跨膜段和可溶性甲基转移酶域,局部存在于内 плазма网膜中.
- 在酵母 (Komagataella phaffii) 中NHMT的重组表达成功甲基化LPMOs,证明其在异质系统中的功能活性.
结论:
- NHMT是线状真菌中LPMOsN终端胺甲基化的关键酶.
- 标志着NHMT的独特结构和内质网膜局部化.
- 重组NHMT的生产使生物技术应用能够创造具有增强稳定性的特异性修饰蛋白和.
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