Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, United States.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Elife. 2020 Oct 16;9:e61886. doi: 10.7554/eLife.61886.
Signaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history of and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs in and other animals may reveal additional new compound families and signaling paradigms.
源自附着于不同代谢构件的信号分子在 和其他线虫的生活史中发挥着核心作用；然而，它们的生物发生的许多方面仍然不清楚。我们使用比较代谢组学表明，介导肠溶酶体相关细胞器 (LRO) 形成的途径对于大多数模块化ascarosides 以及以前未描述的模块化葡萄糖苷的生物合成是必需的。与模块化ascarosides 类似，模块化葡萄糖苷是由核苷、氨基酸、神经递质和脂类代谢中的部分高度选择性组装而来，这表明模块化葡萄糖苷与 ascarosides 一样可能具有信号功能。我们进一步表明，定位于肠细胞器的羧酸酯酶通过酯和酰胺键对于模块化ascarosides 和葡萄糖苷的组装都是必需的。在 和其他动物中进一步探索 LRO 功能和羧酸酯酶同源物可能会揭示更多新的化合物家族和信号范例。
