Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France.
Laboratoire de Chimie des Processus Biologiques, Collège de France, Université Pierre et Marie Curie, CNRS UMR 8229, PSL Research University, 11 Place Marcelin Berthelot, 75005 Paris, France.
Cell Chem Biol. 2019 Apr 18;26(4):482-492.e7. doi: 10.1016/j.chembiol.2018.12.001. Epub 2019 Jan 24.
Ubiquinone (UQ) is a polyprenylated lipid that is conserved from bacteria to humans and is crucial to cellular respiration. How the cell orchestrates the efficient synthesis of UQ, which involves the modification of extremely hydrophobic substrates by multiple sequential enzymes, remains an unresolved issue. Here, we demonstrate that seven Ubi proteins form the Ubi complex, a stable metabolon that catalyzes the last six reactions of the UQ biosynthetic pathway in Escherichia coli. The SCP2 domain of UbiJ forms an extended hydrophobic cavity that binds UQ intermediates inside the 1-MDa Ubi complex. We purify the Ubi complex from cytoplasmic extracts and demonstrate that UQ biosynthesis occurs in this fraction, challenging the current thinking of a membrane-associated biosynthetic process. Collectively, our results document a rare case of stable metabolon and highlight how the supramolecular organization of soluble enzymes allows the modification of hydrophobic substrates in a hydrophilic environment.
泛醌（Ubiquinone，UQ）是一种聚异戊二烯脂质，从细菌到人类都有保留，对细胞呼吸至关重要。细胞如何有效地合成泛醌，其中涉及多个连续酶对极其疏水性底物的修饰，仍然是一个未解决的问题。在这里，我们证明了七种 Ubi 蛋白形成 Ubi 复合物，这是一种稳定的代谢物，可在大肠杆菌中催化泛醌生物合成途径的最后六个反应。UbiJ 的 SCP2 结构域形成一个扩展的疏水性腔，将 UQ 中间产物结合在 1MDa 的 Ubi 复合物内。我们从细胞质提取物中纯化 Ubi 复合物，并证明 UQ 生物合成发生在该部分，这对膜相关生物合成过程的现有观点提出了挑战。总的来说，我们的结果记录了一个罕见的稳定代谢物的案例，并强调了可溶性酶的超分子组织如何允许在亲水环境中修饰疏水性底物。
