This document summarizes the structure and composition of fungal cell walls. It notes that fungal cell walls contain chitin, glucans, mannans, and glycoproteins. Chitin and glucans make up the main structural components. Glucans can be beta-1,3-glucan, beta-1,6-glucan or mixed linkages. Chitin is synthesized by chitin synthase and glucans by the glucan synthase complex. Inhibitors of these enzymes' activities are a target for antifungal drug development.

1. by
Muhammad Getso
Department of Medical Mycology, TUMS-Iran

2. • Fungal cell walls are dynamic structures that are essential for
protection of cellular contents, cell viability, morphogenesis, and
pathogenesis.
• One-fifth of the yeast genome is devoted to the
biosynthesis of the cell wall (e.g. S. cerevisea).
• Fungal cell walls contain chitin, chitosan, β-1,3-glucan, β-
1,6-glucan, mixed β-1,3-/β-1,4-glucan, α-1,3-glucan,
melanin, and glycoproteins as major constituents
• Chitin, along with β-1,3-glucan represents the main structural
components of the fungal cell wall.

3. • The relative proportion of the cell wall polysaccharide can vary according
to cultures conditions, process fermentation, strain background, etc., but s
generally 50 % of the cell wall dry mass is made of β-glucan (10-15 % β-
1,6-glucan).
• The structure and biosynthesis of a fungal cell wall is unique to the fungi,
and is therefore an excellent target for the development of antifungal
drugs.
Fungal cell wall structure
Polysaccharides:
Glucan (50%)
Chitin (3-5%)
Mannan (40%)
Glycoproteins

5. • Chitin, a long linear homopolymer of β-1,4-linked N-
acetylglucosamine.
Glucosamine
Acetyl grp
(150-450 Units)

6. • Chitin accounts for 1–2% of the yeast cell wall (dry weight)
and 10-20% of mycelial cell walls.
• Chitin microfibrils are formed from inter-chain H2- bonding.
They crystallize on EC surface to give enormous tensile
strength and contribute to the overall integrity of the cell wall.
• When chitin synthesis is disrupted, the wall becomes
disordered and the fungus succumbs to osmotic stress

7. • The synthesis of chitin is mediated by chitin synthase, that
catalyzes the transfer of N-acetylglucosamine from UDP-N-
acetylglucosamine to a growing chitin chain.
• Chitin synthesis primarily occurs at sites of active growth and
cell wall remodeling (hyphal apex, tip/neck of bud).
• The elongation of the chitin polymers occurs via ‘vectorial
synthesis’.

8. • The specific roles of the chitin synthases of several fungi have been
studied using both genetic and biochemical analyses.
• S. cerevisiae has 3 chitin synthases: Chs1p, Chs2p and Chs3p.
• Chs1p functions in cell wall repair, replenishing chitin polymers lost
during cytokinesis.
• Chs2p: formation of the primary septum within the dividing yeast
cell.
• Chs3p: generates approximately 80–90% of the total cellular chitin.
• This includes the chitin ring during bud emergence, as well as the
chitin that becomes covalently linked to the beta-1,3-glucan of the
cell wall.

12. • The best-known chitin synthesis inhibitors are nikkomycins
and polyoxins, as well as their synthetic derivatives.
• The nikkomycins and polyoxins are substrate analogs of the
chitin synthase (competitive inhibitors).
• However, they are not effective in controlling mycoses; due to
their limited uptake into the cytoplasm.
• Currently, agents that target the chitin component have found
limited therapeutic use

13. • Glucan is the major structural polysaccharide of the fungal
cell wall, constituting 50–60% of dry weight of the wall.
• It is a polymers of repeating glucose residues assembled
through a variety of chemical linkages.
• 65% - 90% of the cell wall glucan is found to be β-1,3-
glucan.
• Other glucans polymers include:
• β-1,6-glucan
• mixed β-1,3- and β-1,4-glucan
• α-1,3-glucan and
• α-1,4-glucan

14. ≈1500 units
The β-1,3-glucan serves as the main structural constituent to which other
cell wall components are covalently attached.
The synthesis of β-1,3-glucan is required for proper cell wall formation
and fungal development.

15. • Yeast cell walls contain branched β-1,3- and β-1,6-glucans;
where as many filamentous fungi (N. crassa, A. fumigatus) do
not contain β-1,6-glucan
• Glucan polymers are synthesized by membrane associated
enzyme complex; Glucan Synthase Complex (GSC).
• GSC are primarily localized to areas of active growth,
budding or branching.
• The elongation of the chitin polymers occurs via vectorial
synthesis

17. The branched glucans get cross-linked together and to chitin and manno-
proteins to provide the cell wall with mechanical strength and integrity
Glu

18. • The genes encoding for β-1,3-glucan synthase were first
identified in S. cerevisiae, and found to be conserved.
• The gene contains two catalytic subunits (FKS1 and FKS2) and
one regulatory protein, RHO1.
• The FKS1 and RHO1 genes are both essential for survival.

19. • The inhibition of β-1,3-glucan synthesis has been extensively
pursued as a means of disrupting fungal growth and cell wall
formation.
• The echinocandins are non-competitive inhibitors of the β-
1,3-glucan synthase complex.
• Although not fully understood, the echinocandins are known
to bind to the GSC catalytic subunit.
• Treatment with the echinocandins is a promising therapy for
aspergillosis and candidiasis

21. • Gow, N. A., Latge, J. P., & Munro, C. A. (2017). The fungal cell wall:
structure, biosynthesis, and function. Microbiology spectrum.
• Free, S. J. (2013). Fungal cell wall organization and biosynthesis.
In Advances in genetics (Vol. 81, pp. 33-82). Academic Press.
• Latgé, J. P. (2010). Tasting the fungal cell wall. Cellular
microbiology, 12(7), 863-872.
• Bowman, S. M., & Free, S. J. (2006). The structure and synthesis of the
fungal cell wall. Bioessays, 28(8), 799-808.