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Cell Chem Biol. 2019 Apr 18;26(4):482-492.e7. doi: 10.1016/j.chembiol.2018.12.001. Epub 2019 Jan 24.

A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone.

Author information

1
Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France.
2
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.
3
Aix Marseille Université, CNRS, Laboratoire Chimie Bactérienne, Institut Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, Marseille 13009, France.
4
Univ. Grenoble Alpes, CEA, Inserm, BIG-BGE, 38000 Grenoble, France.
5
SOLEIL Synchrotron, L'Orme des Merisiers, 91198 Gif-sur-Yvette, France.
6
Aix Marseille Université, CNRS, Laboratoire Chimie Bactérienne, Institut Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, Marseille 13009, France; SAMe Unit, Department de Microbiologie, Institut Pasteur, 25 Rue du Dr Roux, 75015 Paris, France.
7
Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France. Electronic address: fabien.pierrel@univ-grenoble-alpes.fr.

Abstract

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.

KEYWORDS:

SCP2; bioenergetics; hydroxylation; lipid biosynthesis; membrane; metabolic pathway; metabolon; multiprotein complex; respiration; ubiquinone

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