Biology subjects

Couturier, M.

Publications and source records attributed to Couturier, M..

4 recordsLinked to original sources

bioRxiv2026

A glycosaminoglycan degrading Polysaccharide Utilization Locus in the oral microbiota species Segatella oris

The human gut microbiota has been explored for the last two decades and studies have uncovered its major role in the degradation of complex glycans from the diet as well as the host tissues. Strikingly, until very recently, no similar investigation has been carried out on the human oral cavity microbiota, which is increasingly recognized has an important parameter in gastrointestinal health. Prevotellaceae are an important and under-investigated family of bacteria in both the gut and the oral cavity microbiota. The oral cavity is particularly rich in glycosaminoglycans which could provide an abundant carbon source for the inhabiting microorganisms, and play a significant role in host-pathogen interactions. Hence, we analyzed Polysaccharide Utilization Loci in oral microbiota species and we identified a glycosaminoglycan-degrading Polysaccharide Utilization Locus in Segatella oris. We produced and characterized the four enzymes, confirmed their ability to degrade glycosaminoglycans, and we focused our efforts on the biochemical and structural characterization of the first reported Prevotellaceae endosulfatase.

biochemistry↗

bioRxiv2026

Screening for Polysaccharide Utilization Loci Targeting Marine Polysaccharides

Polysaccharide utilization loci (PULs) have been a goldmine for the characterization of novel carbohydrate active enzymes (CAZymes) and the understanding of their synergistic degradation of complex polysaccharides. We collected PUL predictions containing CAZymes from glycoside hydrolase families GH29, GH50 and GH117, expected to participate in marine polysaccharide breakdown. We explored the evolutionary diversity in these families in terms of sequences and PUL composition, based on sulfatases and CAZymes. From 41 selected PULs, more than 400 putative enzymes were produced, purified and screened on a large collection of carbohydrates. We attributed a function to more than 130 enzymes from five sulfatase subfamilies, 29 known CAZymes families and discovered an activity for 4 families previously of unknown function, including an -L-galactosidase structurally and functionally characterized with mutants. Finally, our detailed analysis of the enzymatic synergies in five PULs, two targeting marine polysaccharides and three targeting eukaryotic polysaccharides, by marine and human gut organisms, highlight the efficiency of our exploratory strategy.

biochemistry↗

bioRxiv2025

Biophysical Modeling Elucidates Mechanistic Principles for Rational Molecular Glue Design

Molecular glues are small molecules that offer a powerful strategy to target previously "undruggable" proteins of interest (POI) by enhancing their interactions with other proteins (effector). Depending on the nature of the effectors, molecular glues can induce stabilizing sequestration or degradation of POI. However, their rational design has been hindered by a poor understanding of how kinetic parameters impact their performance. To address this, we developed a unified mathematical framework that accurately analyzes the dynamics of both glue degraders and stabilizers. Our model reveals that the strong binding affinity of the ternary complex is the key determinant of performance across both modalities, provided that the initial component concentrations and degradation rate constants are fixed. Furthermore, we demonstrate that degrader performance is ultimately limited by its catalytic efficiency and the target proteins natural half-life. We also identify distinct roles for effector abundance, showing that the relative concentrations of the effector and POI are critical for stabilizers but less so for degraders. This quantitative framework provides mechanistic principles for the rationale design and optimization of molecular glues.

molecular biology↗

bioRxiv2022

Transcriptional and translational dynamics underlying heat shock response in the thermophilic Crenarchaeon Sulfolobus acidocaldarius

High-temperature stress is critical for all organisms and induces a profound cellular response. For Crenarchaeota, little information is available on how heat shock affects cellular processes and on how this response is regulated. In this work, we set out to study heat shock response in the thermoacidophilic model crenarchaeon Sulfolobus acidocaldarius, which thrives in volcanic hot springs and has an optimal growth temperature of 75{degrees}C. Pulse-labeling experiments demonstrated that a temperature shift to 86{degrees}C induces a drastic reduction of the transcriptional and translational activity, but that RNA and protein neosynthesis still occurs. By combining RNA sequencing and TMT-labeled mass spectrometry, an integrated mapping of the transcriptome and proteome was performed. This revealed that heat shock causes an immediate change in the gene expression profile, with RNA levels of half of the genes being affected, followed by the more subtle reprogramming of the protein landscape. A limited correlation was observed in differential expression on the RNA and protein level, suggesting that there is a prevalence of post-transcriptional and post-translational regulation upon heat shock. Furthermore, based on the finding that promoter regions of heat shock regulon genes lack a conserved DNA-binding motif, we propose that heat-shock responsive transcription regulation is likely not to be accomplished by a classical transcription factor. Instead, in contrast to histone-harboring Euryarchaeota that have heat-shock transcription factors, it is hypothesized that Sulfolobales and other histone-lacking thermophilic archaea employ an evolutionary ancient mechanism relying on temperature-responsive changes in DNA organization and compaction, induced by the action of nucleoid-associated proteins.

microbiology↗