Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, 9713 AV, the Netherlands.
Interfaculty Mass Spectrometry Center, University of Groningen, 9713 AV, the Netherlands.
Mol Cell. 2022 Jul 21;82(14):2650-2665.e12. doi: 10.1016/j.molcel.2022.05.006. Epub 2022 Jun 3.
Coenzyme A (CoA) is essential for metabolism and protein acetylation. Current knowledge holds that each cell obtains CoA exclusively through biosynthesis via the canonical five-step pathway, starting with pantothenate uptake. However, recent studies have suggested the presence of additional CoA-generating mechanisms, indicating a more complex system for CoA homeostasis. Here, we uncovered pathways for CoA generation through inter-organismal flows of CoA precursors. Using traceable compounds and fruit flies with a genetic block in CoA biosynthesis, we demonstrate that progeny survive embryonal and early larval development by obtaining CoA precursors from maternal sources. Later in life, the microbiome can provide the essential CoA building blocks to the host, enabling continuation of normal development. A flow of stable, long-lasting CoA precursors between living organisms is revealed. This indicates the presence of complex strategies to maintain CoA homeostasis.
辅酶 A（CoA）对代谢和蛋白质乙酰化至关重要。目前的知识认为，每个细胞都只能通过经典的五步途径从生物合成中获得 CoA，从 pantothenate 的摄取开始。然而，最近的研究表明存在额外的 CoA 生成机制，这表明 CoA 动态平衡的系统更为复杂。在这里，我们通过 CoA 前体的种间流动发现了 CoA 生成途径。使用可追踪的化合物和 CoA 生物合成遗传阻断的果蝇，我们证明了后代可以从母体来源获得 CoA 前体，从而在胚胎和早期幼虫发育阶段存活。在生命的后期，微生物组可以为宿主提供必需的 CoA 构建块，从而能够继续正常发育。在生物体之间稳定、持久的 CoA 前体流动被揭示出来。这表明存在维持 CoA 动态平衡的复杂策略。
