Cyclic Glucan Biosynthesis in Gram-Negative Bacteria

Gram-negative bacteria synthesize cyclic β-1,2-glucans (CβGs) as periplasmic or extracellular oligosaccharides that fulfil critical roles in osmoregulation, host–microbe interactions and pathogenicity. These homopolymers comprise glucose monomers linked by β-1,2 glycosidic bonds, cyclised to form ring structures typically containing 15–25 residues. Biosynthesis is catalysed by membrane-bound synthases (often termed Cgs or Opg proteins) that polymerise UDP-activated glucose into linear chains before effecting intramolecular cyclisation. Subsequent modifications—such as succinylation, phosphoglycerolation or phosphoethanolamination—diversify CβG physicochemical properties and mediate interactions with host tissues. A parallel set of glycoside hydrolases remodel glucan chains or process precursors, defining novel enzyme families with unique active-site architectures. Structural studies reveal multi-domain arrangements and unexpected catalytic mechanisms, including long proton-relay pathways and tyrosine-linked intermediates, offering rational targets for antimicrobial intervention and synthetic biology platforms. Beyond physiological functions, engineered pathways in non-pathogenic hosts enable scalable production of CβGs, unlocking applications in drug delivery, nanomaterials and enantiomeric separations.

Research from Nature Portfolio

High-resolution cryo-electron microscopy of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens delineated a multi-domain assembly that catalyses alternating polymerisation and cyclisation steps via a tyrosine-linked oligosaccharide intermediate. This work clarifies the conformational changes that guide chain elongation and ring closure, suggesting avenues to inhibit virulence-associated glucan formation. Complementary structural and functional analyses of two osmo-regulated periplasmic glucan proteins from Escherichia coli identified both a novel glycoside hydrolase family and an unprecedented proton-transfer network. Distinct conformations of paralogous proteins explain differences in enzymatic activity and underscore the diversity of mechanisms by which Gram-negative bacteria regulate glucan synthesis in response to osmotic stress.

Cyclic Glucan Biosynthesis in Gram-Negative Bacteria publication trend

The graph below shows the total number of articles in cyclic glucan biosynthesis in gram-negative bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

Cyclic β-1,2-glucan (CβG): A circular polysaccharide of glucose units joined by β-1,2 glycosidic bonds, found in the periplasm or extracellular milieu of many Gram-negative bacteria.

Osmoregulated periplasmic glucan (OPG): A periplasmic glucan whose synthesis and modification are controlled by environmental osmolarity, often required for cell envelope integrity and signalling.

Transglycosylation: Enzymatic transfer of a glycosyl moiety from one carbohydrate to another without net hydrolysis, often resulting in polymer extension or cyclisation.

Glycoside hydrolase (GH) family: A classification of enzymes that hydrolyse glycosidic bonds, organised into families based on sequence similarity and catalytic mechanism.

Cryo-electron microscopy: A structural biology technique that images flash-frozen specimens with electrons to resolve macromolecular assemblies at near-atomic resolution.

References

1. Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens. Nature Communications (2024).
2. Discovery of Anomer-Inverting Transglycosylase: Cyclic Glucohexadecaose-Producing Enzyme from Xanthomonas, a Phytopathogen. Journal of the American Chemical Society (2024).
3. Identification of enzymatic functions of osmo-regulated periplasmic glucan biosynthesis proteins from Escherichia coli reveals a novel glycoside hydrolase family. Communications Biology (2023).
4. Development of a scalable recombinant system for cyclic beta-1,2-glucans production. Microbial Cell Factories (2024).