UbiE is a bifunctional SAM-dependent C-methyltransferase that catalyzes the penultimate C-methylation step in both ubiquinone (coenzyme Q) and menaquinone (vitamin K2) biosynthesis. The E. coli ortholog was originally identified by Lee et al. (1997), who demonstrated that ubiE mutants fail to catalyze the C-methylation reaction in both pathways PMID:9045837. The same study showed that disruption of ubiE causes accumulation of 2-octaprenyl-6-methoxy-1,4-benzoquinone and demethylmenaquinone as predominant intermediates PMID:9045837.
The yeast ortholog COQ5 was independently characterized by Barkovich et al. (1997), who confirmed C-methyltransferase activity and mitochondrial localization PMID:9083049.
The enzyme has two distinct catalytic activities:
In the mycobacterial ortholog (MenG/Rv0558), Pujari et al. (2022) demonstrated that the actual substrate is the reduced form (demethylmenaquinol), as addition of reductants stimulated activity PMID:36417754.
P. aeruginosa uses ubiquinone-9 (coenzyme Q9) as the primary electron carrier in its aerobic respiratory chain. Matsushita et al. (1980) established that ubiquinone is indispensable for respiratory chain function in P. aeruginosa PMID:6774977. The respiratory chain of aerobically grown P. aeruginosa contains coenzyme Q9 along with b-type and c-type cytochromes PMID:6766443.
Critically, Vo et al. (2020) demonstrated that UQ9 is required for anaerobic denitrification in P. aeruginosa, not just aerobic respiration PMID:32409583. This means that both ubiquinone and menaquinone biosynthesis are physiologically relevant in this organism, and the ubiE C-methylation step is essential for both pathways.
E. coli studies showed that menaquinone (but not demethylmenaquinone) is required for certain anaerobic electron transfer pathways. Tyson et al. (1997) demonstrated that ubiE mutants, which produce demethylmenaquinone but not menaquinone, retain some but not all respiratory activity PMID:9325429. This work also established that menaquinone is essential for cytochrome-c-dependent TMAO reductase and Nrf activities.
In E. coli, ubiE is the first gene of an operon containing ubiE-yigP-ubiB PMID:10960098. In P. aeruginosa PAO1, ubiE (PA5063) is similarly located in a genomic context with genes involved in quinone metabolism, identified through the complete genome sequence PMID:10984043.
The protein belongs to the class I SAM-binding methyltransferase superfamily (IPR029063) with a Rossmann-like fold. It contains the UbiE/COQ5 family signature (IPR004033) and conserved sites (IPR023576) that coordinate SAM binding. The protein has 256 amino acids with SAM-binding residues at positions 79, 100, and 128-129 (UniProt annotation by HAMAP rule MF_01813).
P. aeruginosa ubiE (PA5063) encodes a bifunctional SAM-dependent C-methyltransferase that is required for the C-methylation step in both ubiquinone and menaquinone biosynthesis. Both products are essential for the branched respiratory chain of P. aeruginosa, which uses ubiquinone for both aerobic and anaerobic (denitrification) respiration. The protein is annotated entirely by homology transfer (no direct experimental evidence in P. aeruginosa), but the function is strongly supported by experimental characterization of orthologs in E. coli, yeast, and mycobacteria.