# Fungal Sphingolipids: Biosynthesis Pathways, Structural Features and Biological Functions

**Authors:** Zixin Xue, Liuxi Wang, Chunmei Du

PMC · DOI: 10.3390/jof12020113 · 2026-02-05

## TL;DR

This review explores fungal sphingolipids, their structure, biosynthesis, and roles in cell function and disease, highlighting their potential for antifungal drug development.

## Contribution

The paper provides a comprehensive overview of fungal sphingolipid biology and their therapeutic potential.

## Key findings

- Fungal sphingolipids are involved in cell membrane structure, development, and pathogenicity.
- They play roles in apoptosis and cellular homeostasis.
- Targeting sphingolipid pathways offers potential for antifungal therapies.

## Abstract

Sphingolipids are a class of amphipathic lipids characterized by a sphingoid base backbone, which can be classified into glycosphingolipids and sphingomyelins. They exhibit structural complexity and functional diversity, being widely distributed in eukaryotes and some bacterial species. Sphingolipids are important regulators of signal transduction and cellular homeostasis and are involved in numerous biological processes, including cell polarity establishment, energy metabolism, proliferation, and differentiation. However, research on fungal sphingolipids remains limited. This review provides an overview of sphingolipid species, structural features, and their biosynthesis and degradation in fungi. It also summarizes their essential functions in maintaining cell membrane structure, influencing morphological development, pathogenicity, and homeostasis, and participating in apoptosis. Additionally, the potential of antifungal agents targeting the sphingolipid pathway and their application prospects are discussed. Finally, current challenges and future directions in fungal sphingolipid research are highlighted to support the investigation of their mechanisms and the development of antifungal therapies targeting sphingolipid metabolic pathways.

## Full-text entities

- **Genes:** ORM2 (sphingolipid homeostasis protein ORM2) [NCBI Gene 851064], YPK1 (serine/threonine protein kinase YPK1) [NCBI Gene 853733] {aka SLI2}, TSC3 (Tsc3p) [NCBI Gene 852350], IPT1 (inositolphosphotransferase) [NCBI Gene 851644] {aka KTI6, MIC2, SYR4}, SIT4 (type 2A-related serine/threonine-protein phosphatase SIT4) [NCBI Gene 851513] {aka PPH1}, RAD53 (serine/threonine/tyrosine protein kinase RAD53) [NCBI Gene 855950] {aka LSD1, MEC2, SPK1}, LHS1 (Hsp70 family chaperone LHS1) [NCBI Gene 853789] {aka CER1, SSI1}, FEN2 (Fen2p) [NCBI Gene 850394], YPT7 (Rab family GTPase YPT7) [NCBI Gene 855012] {aka AST4, VAM4}, ACT1 (actin) [NCBI Gene 850504] {aka ABY1, END7}, YDL114W (short-chain dehydrogenase/reductase) [NCBI Gene 851444], XRN1 (chromatin-binding exonuclease XRN1) [NCBI Gene 852702] {aka DST2, KEM1, RAR5, SEP1, SKI1}, MYO5 (myosin 5) [NCBI Gene 855136], GWT1 (glucosaminyl-phosphotidylinositol O-acyltransferase) [NCBI Gene 853354], ELO3 (fatty acid elongase ELO3) [NCBI Gene 851087] {aka APA1, SRE1, SUR4, VBM1}, ELO2 (fatty acid elongase ELO2) [NCBI Gene 850400] {aka FEN1, GNS1, VBM2}, SAC1 (phosphatidylinositol-3-phosphatase SAC1) [NCBI Gene 853668] {aka RSD1}, PKH1 (serine/threonine protein kinase PKH1) [NCBI Gene 852101], ELO1 (fatty acid elongase ELO1) [NCBI Gene 853243], BAR1 (aspartyl protease BAR1) [NCBI Gene 854797] {aka SST1}, YSR3 (sphinganine kinase YSR3) [NCBI Gene 853927] {aka LBP2}, LAG1 (sphingosine N-acyltransferase LAG1) [NCBI Gene 856386], AFT1 (DNA-binding transcription factor AFT1) [NCBI Gene 852809] {aka RCS1}, NCE102 (Nce102p) [NCBI Gene 856272] {aka NCE2}, CAN1 (arginine permease CAN1) [NCBI Gene 856646], LCB2 (serine C-palmitoyltransferase LCB2) [NCBI Gene 851634] {aka SCS1, TSC1}, TSC10 (3-dehydrosphinganine reductase) [NCBI Gene 852568], LCB3 (sphinganine kinase LCB3) [NCBI Gene 853307] {aka LBP1, YSR2}, SUR2 (sphingosine hydroxylase) [NCBI Gene 851891] {aka SYR2}, AUR1 (inositol phosphorylceramide synthase) [NCBI Gene 853866], LCB1 (serine C-palmitoyltransferase LCB1) [NCBI Gene 855342] {aka END8, TSC2}, DPL1 (sphinganine-1-phosphate aldolase DPL1) [NCBI Gene 851888] {aka BST1}
- **Diseases:** injury to (MESH:D014947), PCD (MESH:D003643), SEMD (MESH:D013106), infected (MESH:D007239), toxicity (MESH:D064420), PDR (MESH:D000069279), bipolar disorder (MESH:D001714), Candida infections (MESH:D002177), FAC (MESH:C536560), multiple sclerosis (MESH:D009103), fungal (MESH:D009181), necrosis (MESH:D009336)
- **Chemicals:** mycophenolate (MESH:D009173), AAL (-), H2O2 (MESH:D006861), 3-KDS (MESH:C002882), MIPC (MESH:C068388), AbA (MESH:C071398), Sphingomyelins (MESH:D013109), mannose (MESH:D008358), gangliosides (MESH:D005732), fingolimod (MESH:D000068876), sugar (MESH:D000073893), glycerophospholipid (MESH:D020404), proton (MESH:D011522), PI (MESH:D010716), salt (MESH:D012492), PPMP (MESH:C026733), Rustmicin (MESH:C047784), ceramide-1-phosphate (MESH:C065576), glycan (MESH:D011134), cephalosporins (MESH:D002511), amphotericin B (MESH:D000666), FB1 (MESH:C056933), ergosterol (MESH:D004875), NADP(H) (MESH:D009249), Glycosphingolipid (MESH:D006028), Pleofungins (MESH:C000723924), amino acid (MESH:D000596), nitrogen (MESH:D009584), sialic acid (MESH:D019158), azole (MESH:D001393), GalCer (MESH:D005699), serine (MESH:D012694), carbon (MESH:D002244), DHS (MESH:C005682), phosphatidylcholine (MESH:D010713), fatty acid (MESH:D005227), phospholipids (MESH:D010743), Fluconazole (MESH:D015725), S1P (MESH:C060506), GlcCer (MESH:D005963), IPC (MESH:C477937), palmitoyl-CoA (MESH:D010171), polyenes (MESH:D011090), GPI (MESH:D017261), cerebroside (MESH:D002554), FFAs (MESH:D005230), C26-VLCFA (MESH:C017364), Lipid (MESH:D008055), mannosylinositol phosphorylceramide (MESH:C479822), Khafrefungin (MESH:C109747), Neutral Glycosphingolipids (MESH:D020383), monohexosylceramide (MESH:C013870), iron (MESH:D007501), malonyl-CoA (MESH:D008316), arabinose (MESH:D001089), sterol (MESH:D013261), 2-methyl-benzoic acid (MESH:C009502), Myriocin (MESH:C001996), NAD(H) (MESH:D009243), Sphingolipid (MESH:D013107)
- **Species:** Aspergillus fumigatus (species) [taxon 746128], Schizosaccharomyces pombe (fission yeast, species) [taxon 4896], Paracoccidioides brasiliensis (species) [taxon 121759], Candida albicans (species) [taxon 5476], Scedosporium boydii (species) [taxon 5597], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Pichia kudriavzevii (species) [taxon 4909], Colletotrichum siamense (species) [taxon 690259], Mus musculus (house mouse, species) [taxon 10090], Nakaseomyces glabratus (species) [taxon 5478], Candidozyma auris (species) [taxon 498019], Pyricularia oryzae (rice blast fungus, species) [taxon 318829], Fusarium graminearum (species) [taxon 5518], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Exserohilum turcicum (northern corn leaf blight, species) [taxon 93612], Homo sapiens (human, species) [taxon 9606], Trichoderma reesei (species) [taxon 51453], Mycosarcoma maydis (corn smut, species) [taxon 5270], Rhizoctonia solani (species) [taxon 456999], Komagataella pastoris (species) [taxon 4922], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Gaeumannomyces tritici R3-111a-1 (strain) [taxon 644352], Histoplasma capsulatum (species) [taxon 5037], Aspergillus nidulans (species) [taxon 162425], Dictyostelium discoideum (species) [taxon 44689], Fungi (kingdom) [taxon 4751]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942302/full.md

---
Source: https://tomesphere.com/paper/PMC12942302