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酶激素质素N-和S-甲基化的相反作用

Daniel H Scharf¹, Andreas Habel, Thorsten Heinekamp

¹Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute , Beutenbergstrasse 11a, 07745 Jena, Germany.

Journal of the American Chemical Society

|July 26, 2014

概括

两种甲基转移酶 (MTs) 控制了型二氧化 (ETP) 毒素的活性. 通过S-化,TmtA使ETP无活化,而Glin通过N-甲基化使ETP稳定,从而影响Aspergillus fumigatus的毒性.

科学领域:

微生物学微生物学
生物化学生物化学
菌类学菌类学是指菌类学.

背景情况:

Gliotoxin (1) 是Aspergillus fumigatus的一个关键毒性因子.
类毒素属于类毒素 (ETP) 毒素家族.

研究的目的:

识别和功能性分析涉及ETP毒性的甲基转移酶 (MTs).
阐明这些MT在质毒素生物合成和功能中的作用.

主要方法:

基因组比较和基因淘汰在Aspergillus fumigatus.
在体外酶活性测定S-adenosyl-l-methionine依赖的甲基转移酶.
对ETP稳定性和细胞毒性的分析.

主要成果:

发现TmtA,一种S-adenosyl-l-methionine依赖的S-甲基转移酶,编码在gli基因集群之外.
通过S-化,TmtA通过S-化不可逆地使ETP无活化,这是非ETP生产者可能使用的解毒机制.
鉴定出Glin是一种胺基N-甲基转移酶,通过防止二硫化键的形成来稳定ETP.
通过GliN介导的N-化是 Gliotoxin 生物合成的最后一步,对其细胞毒性至关重要.

结论:

专门的甲基转移酶,TmtA和Glin,对ETP毒素产生相反的作用.
TmtA可以排毒ETP,而Glin通过赋予稳定性并使细胞毒性成为可能来激活ETP.
这些发现揭示了真菌毒素生产和毒性中的关键调节机制.

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