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模块化葡萄糖的组合组合通过碳酸酶调节饥饿生存情况

Chester J J Wrobel¹, Jingfang Yu¹, Pedro R Rodrigues¹

¹Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.

Journal of the American Chemical Society

|August 30, 2021

概括

模块化葡萄糖 (MOGL) 是C. elegans中多样化的代谢物库. 酶Cel-CEST-1.2产生MOGLs,这对于饥饿期间的生存至关重要.

科学领域:

代谢学
生物化学
细菌学

背景情况:

模块化葡萄糖 (MOGL) 是一种新型代谢物.
这些化合物是由C. elegans中的各种代谢前体组装的.
MOGLs的生物合成和功能在很大程度上仍未被描述.

研究的目的:

确定负责MOGL生物合成的酶.
描述这个酶的生化活性.
研究MOGL的生物作用,特别是在饥饿条件下.

主要方法:

通过CRISPR-Cas9进行基因编辑,
对代谢物变化的比较代谢量.
化学合成以确认产品的结构.
在饥饿条件下进行虫养殖和生存测试.

主要成果:

鉴定出Cel- CEST-1.2作为MOGL形成的关键酶.
Cel-CEST-1.2对葡萄糖支架进行特定的2-O-化,产生超过150种不同的MOGL.
生物合成途径在相关的线虫C. briggsae (Cbr-CEST-2) 中保持.
通过饥饿诱导MOGL生物合成和Cel-CEST-1.2表达.
删除Cel-CEST-1.2导致成年C. elegans在饥饿中过早死亡.

结论:

在MOGL的组合生物合成中,Cel-CEST-1.2是关键的酶.
在饥饿期间,MOGL在C. elegans的生存中发挥着至关重要的作用.
这项研究为MOGLs的生物学意义提供了第一个功能性见解.

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