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Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates C. elegans Starvation Survival
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-08-30 , DOI: 10.1021/jacs.1c05908 Chester J J Wrobel 1 , Jingfang Yu 1 , Pedro R Rodrigues 1 , Andreas H Ludewig 1 , Brian J Curtis 1 , Sarah M Cohen 2 , Bennett W Fox 1 , Michael P O'Donnell 3 , Paul W Sternberg 2 , Frank C Schroeder 1
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-08-30 , DOI: 10.1021/jacs.1c05908 Chester J J Wrobel 1 , Jingfang Yu 1 , Pedro R Rodrigues 1 , Andreas H Ludewig 1 , Brian J Curtis 1 , Sarah M Cohen 2 , Bennett W Fox 1 , Michael P O'Donnell 3 , Paul W Sternberg 2 , Frank C Schroeder 1
Affiliation
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The recently discovered modular glucosides (MOGLs) form a large metabolite library derived from combinatorial assembly of moieties from amino acid, neurotransmitter, and lipid metabolism in the model organism C. elegans. Combining CRISPR-Cas9 genome editing, comparative metabolomics, and synthesis, we show that the carboxylesterase homologue Cel-CEST-1.2 is responsible for specific 2-O-acylation of diverse glucose scaffolds with a wide variety of building blocks, resulting in more than 150 different MOGLs. We further show that this biosynthetic role is conserved for the closest homologue of Cel-CEST-1.2 in the related nematode species C. briggsae, Cbr-CEST-2. Expression of Cel-cest-1.2 and MOGL biosynthesis are strongly induced by starvation conditions in C. elegans, one of the premier model systems for mechanisms connecting nutrition and physiology. Cel-cest-1.2-deletion results in early death of adult animals under starvation conditions, providing first insights into the biological functions of MOGLs.
中文翻译：
通过羧酸酯酶组合组装模块化糖苷可调节秀丽隐杆线虫的饥饿生存
最近发现的模块化葡萄糖苷 ( MOGL ) 形成了一个大型代谢物文库，该文库源自模式生物秀丽隐杆线虫中氨基酸、神经递质和脂质代谢的部分组合组装。结合 CRISPR-Cas9 基因组编辑、比较代谢组学和合成，我们表明羧酸酯酶同源物 Cel-CEST-1.2 负责对具有多种构建块的不同葡萄糖支架进行特异性 2- O-酰化，从而产生超过 150不同的 MOGL。我们进一步表明，这种生物合成作用对于相关线虫物种C. briggsae Cbr-CEST-2 中最接近的 Cel-CEST-1.2 同源物是保守的。Cel-cest-1.2的表达和 MOGL 的生物合成是由C. elegans的饥饿条件强烈诱导的， C. elegans是连接营养和生理机制的主要模型系统之一。Cel-cest-1.2缺失导致成年动物在饥饿条件下过早死亡，从而首次了解 MOGL 的生物学功能。
更新日期：2021-09-15
中文翻译：
通过羧酸酯酶组合组装模块化糖苷可调节秀丽隐杆线虫的饥饿生存
最近发现的模块化葡萄糖苷 ( MOGL ) 形成了一个大型代谢物文库，该文库源自模式生物秀丽隐杆线虫中氨基酸、神经递质和脂质代谢的部分组合组装。结合 CRISPR-Cas9 基因组编辑、比较代谢组学和合成，我们表明羧酸酯酶同源物 Cel-CEST-1.2 负责对具有多种构建块的不同葡萄糖支架进行特异性 2- O-酰化，从而产生超过 150不同的 MOGL。我们进一步表明，这种生物合成作用对于相关线虫物种C. briggsae Cbr-CEST-2 中最接近的 Cel-CEST-1.2 同源物是保守的。Cel-cest-1.2的表达和 MOGL 的生物合成是由C. elegans的饥饿条件强烈诱导的， C. elegans是连接营养和生理机制的主要模型系统之一。Cel-cest-1.2缺失导致成年动物在饥饿条件下过早死亡，从而首次了解 MOGL 的生物学功能。
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