Search bioRxiv⌕ Search

bioRxiv · 10.64898/2025.12.12.693890

Deacetylation of β-Mannans by Two Complementary Carbohydrate Esterases from the Human Gut Microbe Bacteroides cellulosilyticus

Abstract

{beta}-Mannans are widespread in the human diet as components of plant-derived foods and as food additives. Several classes of {beta}-mannans are decorated with acetylations, which are key for their physicochemical properties and protection against enzymatic degradation. While the process for depolymerization of acetylated {beta}-mannans has been described in depth for members of the phylum Bacillota, there is limited mechanistic knowledge on how Bacteroidota utilize these glycans. Here, we combined proteomics and biochemical analyses to functionally characterize a pair of carbohydrate esterases (CEs) from Bacteroides cellulosilyticus that, together, deacetylate complex {beta}-mannans. We demonstrate that the newly identified BcCExxx enzyme, representing a novel carbohydrate esterase (CE) family, exhibits high specificity by selectively removing axially oriented 2-O-acetyl groups from mannose residues. In contrast, BcCE7 functions as a broad-spectrum esterase, capable of deacetylating oligosaccharides derived from structurally diverse substrates, including {beta}-mannans, xylans, and acetylated cellulose. In transesterification reactions, BcCExxx showed activity on both mannooligosaccharides and polymeric glucomannan. Overall, our findings provide new insight into the strategies that beneficial Bacteroides have evolved to deacetylate complex {beta}-mannans in the human gut. Significance Statement{beta}-Mannans, commonly found in various plant-based foods and used as food additives, can be metabolized by gut microbes, potentially impacting host health. Acetylation of {beta}-mannans enhances their resistance to enzymatic breakdown, making carbohydrate esterases crucial for gut bacteria to utilize these carbohydrates. This study explores the roles of two carbohydrate esterases (CEs) from a human commensal Bacteroides species in deacetylating complex {beta}-mannans. The two esterases together remove acetylations at different positions on mannose units. BcCE7 is a versatile esterase that deacetylates a variety of oligosaccharides, while the newly discovered BcCExxx is highly active towards 2-O-acetylations on mannose units in both oligosaccharides and polymeric {beta}-mannan. This research enhances our understanding of how Bacteroidota species deacetylate {beta}-mannans.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lindstad, L. J., Mrozek, P. M., Boehlich, J., Leivers, S., Pope, P., La Rosa, S. L., Westereng, B.. 2025-12-12. Deacetylation of β-Mannans by Two Complementary Carbohydrate Esterases from the Human Gut Microbe Bacteroides cellulosilyticus. https://doi.org/10.64898/2025.12.12.693890

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

aaRSID, an engineered pyrrolysyl-tRNA synthetase platform for multi-probe proximity proteomics

Proximity labeling (PL) methods utilize spatially targeted chemical or enzymatic generation of a diffusible, reactive intermediate to covalently tag neighboring proteins in living systems. Unlike other tools for studying molecular interactions, PL can detect transient protein relationships with high spatial and temporal sensitivity, allowing for insight into their roles in biological processes. However, current enzymatic PL tools, such as TurboID and APEX2, are limited by their substrate structure and chemistry, which can generate significant background and/or perturb cellular physiology. To address these limitations, we have developed aminoacyl-tRNA synthetase ID (aaRSID), a PL tool that leverages an engineered pyrrolysyl tRNA synthetase (PylRS) for proximity labeling of proteins. We chose PylRS because it can catalyze promiscuous lysine labeling in the absence of its cognate tRNA and utilize a variety of non-canonical amino acids (ncAAs) as substrates. Here, we demonstrate aaRSID's intrinsic proximity labeling activity, use directed evolution to improve this activity, and apply the improved mutant (aaRSID-Ma1.3) for subcellular proteomics and multiplexed imaging. Our work establishes aminoacyl-tRNA synthetases as a new PL enzyme class and introduces a versatile chemical platform for developing ncAA-derived probes to map cellular microenvironments, greatly expanding the applications possible of PL technology.

biochemistry↗

Cellular uptake of folate-olaparib conjugates via folate receptor-mediated endocytosis: Potential for selective delivery of DNA damage response inhibitors into tumour cells

The folate receptor (FR) is overexpressed in a range of human tumours including ovarian cancer cells. We propose that the overexpression of the FR on the surface of ovarian tumour cells could be exploited for the selective delivery of a DNA damage response inhibitor (DDRi) in the form of an intact folate drug conjugate (FDC). This approach would improve the therapeutic index of the parent DDRi facilitating combination studies of the DDRi-based FDC with DNA damaging chemotherapy. FR-mediated cellular uptake of the proposed folate drug conjugates is requisite for FDC selective delivery into tumours. In this study, we synthesised a series of olaparib-based folate conjugates that maintained the biochemical PARP1 inhibition associated with olaparib and showed binding affinity for the folate receptor. Significantly, we identified compounds 10b and 11 that selectively enter FR overexpressing tumour cells via folate receptor-mediated endocytosis in their intact form and engage with their target as demonstrated by the potent inhibition of PARylation (KB cells, PARylation IC50 = 5.7 and 3.9 nM; respectively).

biochemistry↗

Architecture and Energy Transfer of the Bacterial Photosynthetic Unit

In phototrophic organisms, pigment-protein membrane complexes are densely packed to form photosynthetic units (PSUs) that capture solar energy and convert it into chemical energy. Although the structures of many individual photosynthetic complexes have been resolved, how they are arranged and interact with others within photosynthetic membranes to enable efficient excitation energy transfer (EET) remains poorly understood. Here, we report cryo-electron microscopy structures of PSU supercomplex assemblies from the phototrophic a-proteobacterium Rhodovulum viride, including an RC-LH1 core associated with one or two peripheral LH2 complexes and a curved LH2 tetramer. These membrane-derived assemblies define the relative positions and orientations of neighboring photosynthetic complexes and place their pigment arrays in proximity across antenna-antenna and antenna-core interfaces. Structure-based simulations identify potential EET pathways within the PSU assemblies and reveal rapid energy transfer across both LH2-LH2 and LH2-LH1 interfaces. Collectively, these findings provide insights into the assembly and structural modularity of bacterial PSUs and elucidate how the lateral organization of membrane protein complexes facilitates efficient energy transfer. This work extends structural studies of bacterial photosynthesis from individual complexes to their native higher-order assembly, providing a framework for understanding how photosynthetic supercomplex organization shapes energy migration and for guiding the design of artificial photosynthesis.

biochemistry↗