Biology subjects

Chobert, S.-C.

Publications and source records attributed to Chobert, S.-C..

4 recordsLinked to original sources

bioRxiv2026

UbiB proteins mediate an ATP-dependent decarboxylation step in bacterial ubiquinone biosynthesis

Polyisoprenoid quinones such as ubiquinone (UQ) play an essential role in cellular physiology, acting as membrane-bound electron and proton carriers in respiratory chains and other biological processes across all domains of life. In Escherichia coli, the canonical UQ biosynthesis pathway is well characterized. It involves twelve proteins (UbiA-UbiK and UbiX), most of which catalyzing one of the eight modifications of the aromatic ring derived from 4-hydroxybenzoic acid (4-HB), while others (UbiB, UbiJ, UbiK) act as accessory factors ensuring efficient UQ production. Following prenylation by UbiA and subsequent decarboxylation by the UbiX/UbiD system, the final six reactions are catalyzed within a soluble Ubi-complex. UbiB, an atypical protein kinase-like enzyme, was proposed to extract decarboxylated intermediates from the membrane and mediate their delivery to the Ubi-complex. In this study, we demonstrate the existence of an alternative decarboxylation system in E. coli, as UQ biosynthesis can proceed in the absence of the UbiX/UbiD system. Our results show that this alternative decarboxylation activity depends on UbiB and requires its ATPase activity. Bioinformatic analyses further revealed that approximately 27% of Pseudomonadota species lack UbiX/UbiD homologs, and we found that UbiB proteins from two such species enhance the alternative decarboxylation activity when expressed in E. coli. In addition, we identified conserved residues in UbiB that are specifically required for decarboxylation but dispensable for the delivery of UQ intermediates to the Ubi-complex. Taken together, our findings support a model in which UbiB acts as an ATP-dependent decarboxylase, thereby broadening the functional scope of this poorly characterized protein. ImportancePolyisoprenoid quinones, including ubiquinone (UQ, also known as coenzyme Q), are essential electron and proton carriers in respiratory chains across all domains of life. After prenylation and decarboxylation, the final six steps of UQ biosynthesis are carried out by a soluble Ubi-complex. The only decarboxylation system currently identified in the UQ pathway, the UbiX/UbiD system, is absent from numerous bacterial genomes, and no isofunctional enzymes have been described to date. UbiB, an atypical protein kinase-like enzyme, has been proposed to mediate the extraction of UQ precursors from the membrane, thereby rendering them accessible to the soluble Ubi-complex. Here, we show that UbiB proteins fulfill an additional function in bacteria. Specifically, they contribute to the decarboxylation of UQ precursors through a mechanism that remains unknown but depends on ATP hydrolysis. Given that UbiB is conserved in all UQ-producing bacteria, it may represent a widespread decarboxylation system within this essential metabolic pathway.

biochemistry↗

bioRxiv2026

COCOA-Tree: Phylogenetic visualization and comparative analysis of coevolving residues

The evolutionary co-occurrence of amino acid changes between protein residues underlies key structural and functional properties of protein families. Building on these coevolutionary patterns, methods have been developed to identify groups of residues associated with enzyme functionalities, such as Statistical Coupling Analysis (SCA) or Specificity-Determining Position (SDP) methods. These methods and their variations differ in the metrics used to quantify coevolution, residues weighting schemes, and corrections introduced to mitigate noise and phylogenetic biases. Yet, systematic comparisons across methods are rarely performed, and the evolutionary origins of the coevolutionary patterns highlighted by each approach are seldom addressed, limiting our ability to disentangle functional from phylogenetic contributions. To address these issues, we introduce COCOA-Tree, a Python library for SCA-like dimensionality-reduction analyses. COCOA-Tree supports custom metrics and enables visualization of coevolutionary patterns on phylogenetic trees. We also provide guidance to map results onto 3D structures in PyMOL. Using COCOA-Tree, we reanalyze published datasets and uncover previously unnoticed evolutionary properties of groups of coevolving residues detected by SCA, known as sectors. In particular, in the well-studied S1A serine protease family, we show that two of the three known sectors exhibit qualitatively distinct levels of sequence conservation depending on the enzymatic functions and on the phylogenetic clades to which the proteins belong. We further show that different coevolution metrics often identify qualitatively distinct groups of coevolving residues, although they yield consistent results for mildly conserved residues. Finally, as an example of the versatility of COCOA-Tree, we provide an example of visualizing pairs of residues detected by Direct Coupling Analysis (DCA) methods on a phylogenetic tree, highlighting a rich diversity of co-evolutionary patterns. Overall, we expect COCOA-Tree to help identify residues that control protein function and thereby improve our capacity for functional engineering and our understanding of the principles governing protein evolution. COCOA-Tree website: https://tree-timc.github.io/cocoatree

bioinformatics↗

bioRxiv2025

Global distribution of isoprenoid quinones across Bacteria

Isoprenoid quinones represent a class of redox lipids involved in many critical cellular functions, including ATP synthesis through electron transport chains. They thus occupy a pivotal role in the bioenergetics of all three domains of life. The diversity of quinone types observed across microbial taxa has long supported their use as chemotaxonomic markers in microbial systematics. More recently, variations in quinone repertoires have been linked to metabolic adaptations and a novel quinone was discovered. Despite a revived interest in the role of quinones, a unified perspective on the distribution of quinones in Bacteria is currently lacking. In this study, quinone biosynthetic pathways were systematically annotated in 26,264 high quality genomes of bacterial species, and specific information on quinones produced by over 6,000 bacterial species was extracted by text mining the abstracts of thousands of articles. The results were mapped onto a phylogenetic tree, providing the most comprehensive overview of quinone distribution in Bacteria to date. This enabled us to highlight the surprisingly dynamic evolutionary history of the two menaquinone-producing pathways. Moreover, the identification and experimental validation of a deeply branching ubiquinone pathway in Desulfobacterota represents the first occurrence of such a pathway outside the Pseudomonadota and provides insights into the nature of the ancestral UQ pathway. The updated compendium of bacterial quinones is a valuable resource to facilitate the prediction of quinone structural features from genomic data, to establish correlations between quinone structures and cellular traits, and to explore the evolution of quinone repertoires in connection with the diversification of microbial metabolisms.

microbiology↗

bioRxiv2024

A novel quinone biosynthetic pathway illuminates the evolution of aerobic metabolism

The dominant organisms in modern oxic ecosystems rely on respiratory quinones with high redox potential (HPQs) for electron transport in aerobic respiration and photosynthesis. The diversification of quinones, from low redox potential in anaerobes to HPQs in aerobes, is assumed to have followed Earths surface oxygenation [~]2.3 billion years ago. However, the evolutionary origins of HPQs remain unresolved. Here, we characterize the structure and biosynthetic pathway of a novel ancestral HPQ, methyl-plastoquinone, that is unique to bacteria of the phylum Nitrospirota. Methyl-plastoquinone is structurally related to the two previously known HPQs, plastoquinone from Cyanobacteriota/chloroplasts and ubiquinone from Pseudomonadota/mitochondria, respectively. We demonstrate a common origin of the three HPQ biosynthetic pathways that predates the emergence of Nitrospirota, Cyanobacteriota, and Pseudomonadota. An ancestral HPQ biosynthetic pathway evolved [≥] 3.4 billion years ago in an extinct lineage and was laterally transferred to these three phyla [~]2.5-3.2 billion years ago. We show that Cyanobacteriota and Pseudomonadota were ancestrally aerobic and thus propose that aerobic metabolism using HPQs significantly predates Earths surface oxygenation. Two of the three HPQ pathways were later obtained by eukaryotes through endosymbiosis forming chloroplasts and mitochondria, enabling their rise to dominance in modern oxic ecosystems. Significance statementOxygenic photosynthesis and aerobic respiration by bacteria and eukaryotes rely on respiratory quinones with high redox potential that facilitate membrane-bound electron transport. These quinones are integral to aerobic metabolism and therefore the evolution of aerobic metabolism and quinone biosynthesis must be intertwined. Only two types of high redox potential quinones have been described in bacteria and eukaryotes. Here, we describe the structure and biosynthetic pathway of a third type, methyl-plastoquinone, that is exclusive to bacteria of the phylum Nitrospirota. We then use phylogenetic analysis to show that the three high redox potential quinones have a single evolutionary origin and are much older than previously considered, predating the Great Oxygenation Event, when significant amounts of O2 first accumulated in the atmosphere.

microbiology↗