Fungal beta-1,3-glucan synthesis at the plasma membrane

Beta-1,3-glucan is the main structural polysaccharide of most fungal cell walls and septa. It is made at the plasma membrane by glucan synthase, a multi-pass GT48 (FKS family) glycosyltransferase. The synthase transfers glucose from cytosolic UDP-glucose to the growing chain at an active site on the cytosolic face and threads the chain through a transmembrane channel into the wall. The small GTPase Rho1 is the regulatory subunit: GTP-bound Rho1 binds the synthase and is needed for its activity. Many fungi have several synthase paralogs with distinct jobs. Saccharomyces cerevisiae has Fks1 and Gsc2/Fks2. Schizosaccharomyces pombe has four: Bgs1 makes the linear beta-1,3-glucan of the primary septum, Bgs4 makes the major branched beta-1,3-glucan of the wall and secondary septum, Bgs2 acts in the spore wall, and Bgs3 is essential but its product is less well defined. Bgs3 works with Ghs2, a Kre6-related membrane protein with an extracellular GH16 domain. In the current model Ghs2 adds beta-1,6-linked branches to the chain Bgs3 extrudes, but that reaction has not been assayed. UDP-glucose supply, synthase trafficking and localization factors, Rho1 GEFs and GAPs, and later cross-linking and remodeling of wall glucan by GH72/GH16/GH17 enzymes are outside the module.

MODULE:fungal_beta_1_3_glucan_synthesisDRAFTCONCRETEMetabolic Pathwaymodules/fungal_beta_1_3_glucan_synthesis.yaml

fungal-type cell wall (1->3)-beta-D-glucan biosynthetic processGO:0071970

GO:0071970

fungal-type cell wall (1->3)-beta-D-glucan biosynthetic process

Module-level process concept.

PMID:36949198

Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1.

Cryo-EM structures of S. cerevisiae Fks1 place the active site at the membrane-cytoplasm interface and show a glucan path across the membrane.

These structures reveal the active site of the enzyme at the membrane-cytoplasm interface and a glucan translocation path spanning the membrane bilayer.

PMID:40021629

Cryo-EM structure of the β-1,3-glucan synthase FKS1-Rho1 complex.

Structure of the Fks1-Rho1 holoenzyme. Rho1 sits between the GT domain and TM7-15, and binding is enhanced by GTPgammaS.

The GS holoenzyme comprises the glycosyltransferase FKS1 and its regulatory factor Rho1, a small GTPase.

PMID:34959732

Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity.

Summary of the S. pombe synthases: linear septum glucan from Bgs1, branched wall glucan from Bgs4, Bgs3 essential with unknown function. This is the definition reference for GO:0140752 and GO:0140753.

Bgs3 is essential, although its function remains unknown

PMID:42786154

A bipartite glucan synthase-remodeler module organizes branched glucan assembly in the fungal cell wall.

Ghs2 is an obligate partner of Bgs3 and is proposed to branch the nascent Bgs3 chain. Sbg1 is the analogous partner of Bgs1.

these findings support a model in which Bgs3 synthesizes linear β-1,3-glucan and Ghs2 subsequently introduces β-1,6-linked branch points onto the nascent polymer

file:SCHPO/bgs3/bgs3-bioinformatics/RESULTS.md

Re-analysis of the deposited AlphaFold3 Ghs2-Bgs3 model (PMID:42786154)

In the authors' deposited AlphaFold3 model, the Ghs2-Bgs3 TM-TM interface is confident, but the GH16 position relative to the Bgs3 extrusion pore is not. The module therefore does not encode a structural placement.

AF3 does not know where the GH16 domain sits relative to Bgs3

8Nodes

3Parts

1Variant Sets

4Variants

6Annotons

2Connections

Derived QC

Recommended-field compliance

80.0% recommended fields populated

knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

No MODULE:fungal_beta_1_3_glucan_synthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 9 evidence or coverage gap(s) (12 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
rho1_activity	RHO1 (Saccharomyces cerevisiae) UniProtKB:P06780 Family Representative	GTPase activity GO:0003924	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
rho1_activity	rho1 (Schizosaccharomyces pombe) UniProtKB:Q09914 Family Representative	GTPase activity GO:0003924	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fks1_activity	FKS1 (Saccharomyces cerevisiae) UniProtKB:P38631 Family Representative	1,3-beta-D-glucan synthase activity GO:0003843	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
fks1_activity	GSC2/FKS2 (Saccharomyces cerevisiae) UniProtKB:P40989 Family Representative	1,3-beta-D-glucan synthase activity GO:0003843	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
bgs1_activity	bgs1 (Schizosaccharomyces pombe) UniProtKB:Q10287 Family Representative	linear 1,3-beta-D-glucan synthase activity GO:0140753	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bgs4_activity	bgs4 (Schizosaccharomyces pombe) UniProtKB:O74475 Family Representative	branched 1,3-beta-D-glucan synthase activity GO:0140752	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bgs3_activity	bgs3 (Schizosaccharomyces pombe) UniProtKB:Q9P377 Family Representative	1,3-beta-D-glucan synthase activity GO:0003843	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rho1_activity	Rho1 subfamily of Rho GTPases PANTHER:PTHR24072:SF168 Family	GTPase activity GO:0003924	Family Function Unreviewed Family review leaves GO:0003924 UNRESOLVED. Full-length RHOJ is directly demonstrated to hydrolyze GTP, so RHOJ must not be labelled GTPase-deficient simply by analogy to atypical Rnd proteins. The benchmark product has a disrupted distal sequence and cannot inherit intact RHOJ kinetics. Across the broader family, nucleotide regulation and catalytic competence require branch- and product-specific evidence.
fks1_activity	Fks1-related glucan synthase subfamily PANTHER:PTHR12741:SF48 Family	1,3-beta-D-glucan synthase activity GO:0003843	Family Review Missing No supported structured family review is available for PANTHER:PTHR12741:SF48.
bgs1_activity	Bgs1 subfamily PANTHER:PTHR12741:SF105 Family	linear 1,3-beta-D-glucan synthase activity GO:0140753	Family Review Missing No supported structured family review is available for PANTHER:PTHR12741:SF105.
bgs4_activity	Bgs4 subfamily PANTHER:PTHR12741:SF109 Family	branched 1,3-beta-D-glucan synthase activity GO:0140752	Family Review Missing No supported structured family review is available for PANTHER:PTHR12741:SF109.
bgs3_activity	Bgs3 subfamily PANTHER:PTHR12741:SF100 Family	1,3-beta-D-glucan synthase activity GO:0003843	Family Review Missing No supported structured family review is available for PANTHER:PTHR12741:SF100.

Gene-review completeness (4/8 grounded genes reviewed)

4 complete review(s) · 0 with deep research · 4 missing review · 4 reviewed but lacking deep research

Gene	Review	Complete	Deep research
bgs1 Q10287	✓	✓	✗
bgs3 Q9P377	✓	✓	✗
bgs4 O74475	✓	✓	✗
RHO1 (Saccharomyces cerevisiae) P06780	✗	—	—
FKS1 (Saccharomyces cerevisiae) P38631	✗	—	—
GSC2/FKS2 (Saccharomyces cerevisiae) P40989	✗	—	—
rho1 (Schizosaccharomyces pombe) Q09914	✗	—	—
SPAC17G6.11c O13789	✓	✓	✗

Tree

Fungal beta-1,3-glucan synthesis at the plasma membraneMetabolic Pathwayfungal_beta_1_3_glucan_synthesis

Parts
1. 1. activation of the glucan synthase by GTP-bound Rho1
2. Rho1-GTP activation of beta-1,3-glucan synthaseRegulatory Steprho1_activation
  
  Annotons
  - Rho1 GTPase, regulatory subunit of glucan synthase Family: Rho1 subfamily of Rho GTPases
3. 2. beta-1,3-glucan polymerisation and extrusion
4. UDP-glucose + (1->3)-beta-D-glucan(n) to (1->3)-beta-D-glucan(n+1) + UDPReactionglucan_polymerisation
  
  Variants
  1. GT48 glucan synthase paralogs with distinct products and locations by synthase subfamily and cellular role (One Or More)
    
    Fks1/Gsc2-type synthase (S. cerevisiae)Reactionfks1_type_variant
    
    Annotons
    
    Fks1/Gsc2 catalytic subunit Family: Fks1-related glucan synthase subfamily
    
    Bgs1-type linear septum glucan synthaseReactionbgs1_septum_variant
    
    Annotons
    
    Bgs1 catalytic subunit Family: Bgs1 subfamily
    
    Bgs4-type branched wall glucan synthaseReactionbgs4_branched_variant
    
    Annotons
    
    Bgs4 catalytic subunit Family: Bgs4 subfamily
    
    Bgs3 synthase with its Ghs2 partnerReactionbgs3_ghs2_variant
    
    Annotons
    
    Bgs3 catalytic subunit Family: Bgs3 subfamily
5. 3. proposed branching of the nascent Bgs3 chain by Ghs2 optional
6. Proposed beta-1,6 branching of nascent beta-1,3-glucanReactionnascent_glucan_branching
  
  Annotons
  - Ghs2 GH16 domain (activity unassayed) Family: Kre6/Skn1-related GH16 membrane proteins

Details

Context

fungiNCBITaxon:4751

Fungal beta-1,3-glucan synthesis at the plasma membraneMetabolic Pathwayfungal_beta_1_3_glucan_synthesis

fungal-type cell wall (1->3)-beta-D-glucan biosynthetic processGO:0071970

Context

fungiNCBITaxon:4751

NEW module (2026-11), built after reviewing S. pombe bgs1, bgs3, bgs4 and Ghs2 (SPAC17G6.11c). Boundary decisions: (1) Rho1 is inside because it is a structural regulatory subunit of the holoenzyme (PMID:8602515, PMID:40021629). Its GEFs (Rgf1, Rgf3) and other effectors are outside. (2) Synthase partners that only control trafficking or localization (Sbg1 for Bgs1, Smi1, exomer, TRAPP-II, Myo52) are outside. Ghs2 is inside, as an optional third part, because its GH16 catalytic residues are needed and its loss reduces branched glucan, so it is proposed to modify the product, not just deliver the synthase. (3) S. pombe Bgs2 (spore wall) shares PANTHER subfamily SF48 with Fks1/Gsc2 and is mentioned, not modelled. (4) alpha-1,3-glucan (fungal_alpha_1_3_glucan_synthesis: Ags1 with Aah1/Aah3) and chitin (fungal_chitin_chitosan_synthesis) are separate modules. The linear/branched split of GO:0003843 (GO:0140753, GO:0140752) rests on the wall composition of mutants. The Bgs3-Ghs2 finding that a separate GH16 protein makes branches calls into question whether any synthase is itself "branched". This is recorded as a knowledge gap, not changed here.

Connections

rho1_activation -> glucan_polymerisation Positively Regulates

Rho1-GTP activates the GT48 synthase (all four S. pombe Bgs subunits; Fks1/Gsc2).

bgs3_ghs2_variant -> nascent_glucan_branching Provides Input For

Proposed: Ghs2 branches the beta-1,3-glucan chain extruded by Bgs3 (PMID:42786154). Not shown for the other variants.

Part 1: activation of the glucan synthase by GTP-bound Rho1

Rho1-GTP activation of beta-1,3-glucan synthaseRegulatory Steprho1_activation

Annotons

Rho1 GTPase, regulatory subunit of glucan synthase

rho1_activity

Participant: Family: Rho1 subfamily of Rho GTPases

Family:

Rho1 subfamily of Rho GTPasesPANTHER:PTHR24072:SF168

Representative Members: RHO1 (Saccharomyces cerevisiae)UniProtKB:P06780 rho1 (Schizosaccharomyces pombe)UniProtKB:Q09914

Function

GTPase activityGO:0003924 In the GTP-bound state, binds the synthase between its GT domain and transmembrane helices and switches it to the active state.

Locations

plasma membraneGO:0005886

Non-catalytic regulatory subunit of glucan synthase. Rho1 has other effectors (e.g. Pkc1, formins); only its synthase activation is part of this module.

PMID:8602515

Rho1 restores glucan synthase activity of rho1-ts membranes and binds Fks1 in vivo.

Therefore, it appears that Rho1p is a regulatory subunit of beta(1-->3)glucan synthase.

PMID:9372443

S. pombe Rho1 directly activates the glucan synthase.

The Schizosaccharomyces pombe rho1p GTPase directly activates the (1-3) beta-D-glucan synthase

PMID:35049972

Rho1 activates all four S. pombe catalytic subunits.

the essential GTPase Rho1 is the β-GS regulatory subunit responsible for the activation of GS catalytic subunits Bgs1 to Bgs4

Part 2: beta-1,3-glucan polymerisation and extrusion

UDP-glucose + (1->3)-beta-D-glucan(n) to (1->3)-beta-D-glucan(n+1) + UDPReactionglucan_polymerisation

Variant set: GT48 glucan synthase paralogs with distinct products and locations by synthase subfamily and cellular role (One Or More)

All catalyse the EC 2.4.1.34 reaction (PAINT places GO:0003843 at PTN001272353, a Dikarya node) but belong to different PANTHER subfamilies and build different structures. GO's linear (GO:0140753) and branched (GO:0140752) synthase activities describe the product, as inferred from mutant wall composition. No purified synthase has been shown to make branches itself.

Fks1/Gsc2-type synthase (S. cerevisiae)Reactionfks1_type_variant

Annotons

Fks1/Gsc2 catalytic subunit

fks1_activity

Participant: Family: Fks1-related glucan synthase subfamily

Family:

Fks1-related glucan synthase subfamilyPANTHER:PTHR12741:SF48

Representative Members: FKS1 (Saccharomyces cerevisiae)UniProtKB:P38631 GSC2/FKS2 (Saccharomyces cerevisiae)UniProtKB:P40989

Required Function:

1,3-beta-D-glucan synthase activityGO:0003843

Function

1,3-beta-D-glucan synthase activityGO:0003843

Substrates: UDP-alpha-D-glucose (1->3)-beta-D-glucan (n residues)

Products: (1->3)-beta-D-glucan (n+1 residues) UDP

Processes

fungal-type cell wall (1->3)-beta-D-glucan biosynthetic processGO:0071970

Locations

plasma membraneGO:0005886

Redundant pair in budding yeast. Fks1 dominates in vegetative growth. S. pombe Bgs2 (UniProtKB:O13967, spore wall) falls in the same PANTHER subfamily but is not modelled here.

Bgs1-type linear septum glucan synthaseReactionbgs1_septum_variant

Annotons

Bgs1 catalytic subunit

bgs1_activity

Participant: Family: Bgs1 subfamily

Family:

Bgs1 subfamilyPANTHER:PTHR12741:SF105

Representative Members: bgs1 (Schizosaccharomyces pombe)UniProtKB:Q10287

Required Function:

linear 1,3-beta-D-glucan synthase activityGO:0140753

Function

linear 1,3-beta-D-glucan synthase activityGO:0140753

Processes

primary cell septum biogenesisGO:0031671

Locations

cell division siteGO:0032153

First synthase at the division site, recruited next to the contractile ring. Its trafficking needs the TM partner Sbg1, which is outside the module (PMID:42786154).

Bgs4-type branched wall glucan synthaseReactionbgs4_branched_variant

Annotons

Bgs4 catalytic subunit

bgs4_activity

Participant: Family: Bgs4 subfamily

Family:

Bgs4 subfamilyPANTHER:PTHR12741:SF109

Representative Members: bgs4 (Schizosaccharomyces pombe)UniProtKB:O74475

Required Function:

branched 1,3-beta-D-glucan synthase activityGO:0140752

Function

branched 1,3-beta-D-glucan synthase activityGO:0140752

Processes

fungal-type cell wall (1->3)-beta-D-glucan biosynthetic processGO:0071970 secondary cell septum biogenesisGO:1990344

Locations

plasma membraneGO:0005886

Main synthase for wall integrity and the main echinocandin target in S. pombe. Whether Bgs4 makes branch points itself or relies on a partner, as Bgs3 does, is unknown.

Bgs3 synthase with its Ghs2 partnerReactionbgs3_ghs2_variant

Annotons

Bgs3 catalytic subunit

bgs3_activity

Participant: Family: Bgs3 subfamily

Family:

Bgs3 subfamilyPANTHER:PTHR12741:SF100

Representative Members: bgs3 (Schizosaccharomyces pombe)UniProtKB:Q9P377

Required Function:

1,3-beta-D-glucan synthase activityGO:0003843

Function

1,3-beta-D-glucan synthase activityGO:0003843 Kept at the parent term. The 2026 model has Bgs3 making linear chains, but its product has not been analysed directly.

Processes

fungal-type cell wall (1->3)-beta-D-glucan biosynthetic processGO:0071970

Locations

cell tipGO:0051286 cell division siteGO:0032153

Essential synthase whose localization depends on Ghs2, and vice versa (PMID:42786154).

Part 3: proposed branching of the nascent Bgs3 chain by Ghs2 (optional)

Proposed beta-1,6 branching of nascent beta-1,3-glucanReactionnascent_glucan_branching

Optional, and so far shown only for the S. pombe Bgs3-Ghs2 pair. The reaction is inferred from the GH16 domain, the need for its catalytic glutamates, and loss of branched glucan in ghs2 mutants. It has not been assayed.

Annotons

Ghs2 GH16 domain (activity unassayed)

ghs2_branching

Participant: Family: Kre6/Skn1-related GH16 membrane proteins

Family:

Kre6/Skn1-related GH16 membrane proteinsPANTHER:PTHR31361

Representative Members: Ghs2 / SPAC17G6.11c (Schizosaccharomyces pombe)UniProtKB:O13789

Processes

fungal-type cell wall beta-glucan biosynthetic processGO:0070880

Locations

plasma membraneGO:0005886

No molecular function is asserted; see the proposed new term in the SPAC17G6.11c review. Budding-yeast Kre6 is in the same family but has not been shown to bind Fks1, so it is not a representative member.

PMID:42786154

Ghs2 is required specifically for Bgs3 localization.

These findings indicate that Ghs2 is specifically required for the proper subcellular localization of Bgs3, but not other glucan synthases.