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© Research
Publication : Cell chemical biology

A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell chemical biology - 24 Jan 2019

Hajj Chehade M, Pelosi L, Fyfe CD, Loiseau L, Rascalou B, Brugière S, Kazemzadeh K, Vo CD, Ciccone L, Aussel L, Couté Y, Fontecave M, Barras F, Lombard M, Pierrel F

Link to Pubmed [PMID] – 30686758

Cell Chem Biol 2019 Apr;26(4):482-492.e7

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.

https://www.ncbi.nlm.nih.gov/pubmed/30686758