Global distribution of isoprenoid quinones across Bacteria

Isoprenoid quinones are redox-active lipids essential for numerous cellular processes, including ATP synthesis via electron transport chains. They are found across all domains of life. Their diversity among microbial taxa has established them as chemotaxonomic markers, while recent studies have linked quinone repertoire variations to metabolic adaptations, and have identified novel quinone types. Despite this renewed interest, a comprehensive overview of quinone distribution across Bacteria is missing. Here, we systematically annotated quinone biosynthetic pathways for major quinones (ubiquinone, rhodoquinone, plastoquinone, and menaquinone) across 26,264 high-quality bacterial genomes. We also text-mined quinone data from over 6,000 species in published abstracts to validate our genomic annotations while compiling valuable information on quinone chains. Mapping these data onto a phylogenetic framework provides the most extensive synthesis of quinone distribution in Bacteria to date. Our analysis reveals an unexpectedly dynamic evolutionary history for the two menaquinone-producing pathways. Furthermore, the discovery and experimental validation of a deeply branching ubiquinone pathway in the phylum Desulfobacterota provide the first evidence of such a pathway outside the phylum Pseudomonadota, offering new insights into the nature of the ancestral ubiquinone biosynthetic route. Beyond these discoveries, the global overview of bacterial quinones distribution presented here paves the way for future investigations into quinone-associated biochemistry and physiology, including predicting quinone structural features from genomic data, exploring correlations between quinone structures and cellular traits, and studying quinone repertoire evolution in relation to microbial metabolic diversification.IMPORTANCEIsoprenoid quinones are small electron-carrying molecules found in the membranes of organisms that produce energy through photosynthesis or respiration and participate in other important cellular processes. Recent advances in the characterization of their biosynthesis pathways enable their automated annotation from genome analyses. In this article, we performed the genomic analysis of over 26,000 cultured and uncultured bacteria, which was complemented by literature data compiled on over 6,000 cultured bacteria. This enabled us to provide an unprecedented overview of quinone distribution across the bacterial diversity. Creating such a comprehensive data set revealed new information about quinone distribution and evolutionary paths and will facilitate future exploration of various aspects of quinone biology, including their role in the evolution and diversification of bacterial metabolism.