Glycogen and Polysaccharide Metabolism in Mycobacterial Systems

Mycobacterial species deploy intricate pathways to synthesise and remodel glycogen-like α-glucans and complex polysaccharides that underpin both energy storage and pathogenicity. Intracellular glycogen-like polymers are assembled via the canonical GlgC–GlgA route and a specialised trehalose-dependent GlgE pathway, the latter channelled through a series of enzymes including TreS, Pep2, maltokinase (Mak), GlgE and GlgB. A separate Rv3032 route contributes to methylglucose lipopolysaccharide formation, linking polysaccharide biosynthesis to lipid metabolism. Some α-glucan is exported to form a protective capsule that mediates immune evasion and host colonisation. Enzymatic branching and debranching regulate polymer solubility and availability, while trehalose cycling interconnects structural and storage roles. Together, these metabolic networks present vulnerabilities for anti-tubercular strategies and inform biotechnological applications in carbohydrate engineering.

Research from Nature Portfolio

Recent studies have completed the structural ensemble of the GlgE pathway by resolving the three-dimensional fold of mycobacterial maltokinase at atomic resolution. This eukaryotic-like kinase bears a novel N-terminal domain that modulates phosphate binding and likely anchors to the upstream trehalose-maltose isomerase, illuminating regulatory crosstalk within the pathway. By providing an all-atom map of Mak in complex with non-hydrolysable ATP analogues, this work enables structure-guided inhibitor design targeting an enzyme essential for turning over α-maltose-1-phosphate, thereby opening new avenues for anti-tubercular compound development.

Glycogen and Polysaccharide Metabolism in Mycobacterial Systems publication trend

The graph below shows the total number of articles in glycogen and polysaccharide metabolism in mycobacterial systems across all publications each year (not limited to Nature Index journals).

Technical terms

α-Glucan: A glucose polymer with α-1,4 linkages and α-1,6 branches, resembling bacterial glycogen.

GlgE pathway: A four-step trehalose-to-glycogen biosynthetic route involving TreS, Pep2, Mak and GlgE.

Maltokinase (Mak): An eukaryotic-like kinase that phosphorylates maltose to α-maltose-1-phosphate.

GlgB: The branching enzyme that introduces α-1,6 linkages into linear glucan chains.

Stealth protein (CpsY): A mycobacterial enzyme that synthesises capsular polysaccharides to subvert host immunity.

Trehalose: A disaccharide precursor that feeds into both storage glycogen and structural polymer pathways.

References

1. Structural and Functional Insights into the Stealth Protein CpsY of Mycobacterium tuberculosis. Biomolecules (2023).
2. Metabolic Network for the Biosynthesis of Intra- and Extracellular α-Glucans Required for Virulence of Mycobacterium tuberculosis. PLOS Pathogens (2016).
3. Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway. Scientific Reports (2015).