Chitin Biosynthesis in Yeast Cell Walls

Chitin is a linear polymer of β-1,4-linked N-acetylglucosamine that confers rigidity and structural integrity to fungal cell walls. In yeast, chitin deposition occurs at specialised sites such as bud scars and the septum, contributing to cell shape, division and stress resistance. Biosynthesis is catalysed by membrane-embedded chitin synthases (Chs), which transfer N-acetylglucosamine from the activated donor UDP-GlcNAc to the growing polymer and concomitantly translocate the chain across the plasma membrane. Three principal isoforms, Chs1, Chs2 and Chs3, differ in temporal expression, localisation and catalytic properties. Chs3 accounts for the bulk of cell-wall chitin and undergoes tightly regulated intracellular trafficking through the endoplasmic reticulum, Golgi apparatus, secretory vesicles and endosomal recycling pathways. Activity of these enzymes is controlled by substrate availability, self-priming mechanisms, complex formation and feedback from cell-wall integrity sensors. Disruption of chitin biosynthesis impairs morphogenesis and renders yeast vulnerable to lytic agents, underscoring its appeal as an antifungal target.

Research from Nature Portfolio

Advances in cryo-electron microscopy have elucidated multiple conformational states of chitin synthases from Saccharomyces cerevisiae and Phytophthora sojae. High-resolution structures of a yeast synthase in apo, substrate-bound and inhibitor-bound forms reveal how UDP-GlcNAc and acceptor substrates occupy the active site, how a swinging loop controls entry to a transmembrane channel, and how peptidyl nucleoside compounds block catalysis. Complementary studies on PsChs1 capture sequential stages of chitin chain initiation, elongation and release, defining a reaction chamber with distinct binding, catalytic and polymer-translocation domains. These models clarify the directional, multistep mechanism of chain synthesis and discharge, and provide a structural framework for rational inhibitor design aimed at blocking fungal growth.

Chitin Biosynthesis in Yeast Cell Walls publication trend

The graph below shows the total number of articles in chitin biosynthesis in yeast cell walls across all publications each year (not limited to Nature Index journals).

Technical terms

Chitin: A linear homopolymer of β-1,4-linked N-acetylglucosamine units forming structural fibres in fungal cell walls.

Chitin Synthase: A membrane-integrated glycosyltransferase enzyme that polymerises chitin from UDP-GlcNAc and translocates the chain across the membrane.

UDP-GlcNAc: Uridine diphosphate N-acetylglucosamine, the activated sugar nucleotide donor for chitin polymerisation.

N-acetylglucosamine (GlcNAc): The monosaccharide building block of chitin, derived from fructose-6-phosphate via an aminotransferase pathway.

Cryo-electron Microscopy (Cryo-EM): A structural biology technique that images vitrified specimens at near-atomic resolution to visualise protein conformations.

Transmembrane Channel: A conduit formed by chitin synthase through which the elongating polymer is extruded to the cell exterior.

References

1. Structure, catalysis, chitin transport, and selective inhibition of chitin synthase. Nature Communications (2023).
2. Structural basis for directional chitin biosynthesis. Nature (2022).
3. Fungal cell wall: An underexploited target for antifungal therapies. PLOS Pathogens (2021).
4. Chitin Synthesis in Yeast: A Matter of Trafficking. International Journal of Molecular Sciences (2022).
5. Priming and elongation of chitin chains: Implications for chitin synthase mechanism. The Cell Surface (2018).