Methyl ketone (MK)-ascarosides represent essential components of several pheromones in , including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the β-keto acyl-CoA side chain of an ascaroside intermediate during β-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The β-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, ). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm.

中文翻译：

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酰基辅酶A硫酯酶对于秀丽隐杆线虫中关键的多尔信息素的生物合成至关重要

甲基酮 (MK)-蛔苷是多种信息素的重要组成部分，包括引发抗应激性幼虫阶段的多尔信息素和吸引雄性的性信息素。在这里，我们鉴定了 MK-蛔苷生物合成所需的酰基辅酶 A 硫酯酶 ACOT-15。我们提出了一个模型，其中 ACOT-15 在 β-氧化过程中水解蛔苷中间体的 β-酮酰基-CoA 侧链，导致脱羧并形成 MK。通过比较代谢组学，我们确定了其他 ACOT-15 依赖性代谢物，包括一种不寻常的哌啶基修饰的蛔苷，让人想起生物碱pellierine。ACOT-15 产生的 β-酮酸可能与 1-哌啶偶联生成哌啶基蛔苷，其诱导性远低于 dauer 信息素 asc-C6-MK (ascr#2, )。提供的细菌食物会影响蠕虫产生哌啶基蛔苷。我们的工作展示了 MK- 和哌啶基蛔苷的生物合成如何交叉以及细菌食物如何影响蠕虫中的化学信号传导。