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Microorganisms
Volume 13
Issue 4
10.3390/microorganisms13040862
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Review

Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development

by
Lingyun Song
1,†,
Sha Wang
2,†,
Hang Zou
3,
Xiaokang Yi
1,
Shihan Jia
1,
Rongpeng Li
1,* and
Jinxing Song
1,4,*
1
The Key Laboratory of Biotechnology for Medicinal and Edible Plant Resources of Jiangsu Province, School of Life Sciences, Jiangsu Normal University, Xuzhou 221116, China
2
Huzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou 313000, China
3
Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Chengdu University, Chengdu 610059, China
4
Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Science, Institute of Drug Discovery Technology, Ningbo 315211, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2025, 13(4), 862; https://doi.org/10.3390/microorganisms13040862
Submission received: 24 February 2025 / Revised: 22 March 2025 / Accepted: 3 April 2025 / Published: 10 April 2025
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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Abstract

Ergosterol plays a dual role in fungal pathogenesis and azole resistance, driving key advancements in the understanding of its biosynthesis regulation. This review integrates the latest research progress on the regulation of fungal ergosterol biosynthesis and its role in drug resistance and pathogenicity. We comprehensively discuss the functions of key enzymes (such as Erg11p/Cyp51A, Erg6p, Erg3p, and Erg25p) in the mevalonate, late, and alternative pathways. Notably, we highlight the complex regulation of cyp51A expression by factors such as SrbA, AtrR, CBC, HapX, and NCT in Aspergillus fumigatus, and elucidate the distinctive roles of Upc2, Adr1, and Rpn4 in Candida species. Importantly, we summarize recent discoveries on the CprA-dependent regulation of Cyp51A/Erg11p and heme-mediated stability control. Based on these findings, we propose innovative antifungal strategies, including dual-target inhibition and multi-enzyme inhibition by natural products, which provide novel insights and potential directions for the development of next-generation antifungal therapies.
Keywords: ergosterol biosynthesis; pathogenic fungi; Aspergillus fumigatus; antimicrobial resistance; erg11A/cyp51A ergosterol biosynthesis; pathogenic fungi; Aspergillus fumigatus; antimicrobial resistance; erg11A/cyp51A

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MDPI and ACS Style

Song, L.; Wang, S.; Zou, H.; Yi, X.; Jia, S.; Li, R.; Song, J. Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development. Microorganisms 2025, 13, 862. https://doi.org/10.3390/microorganisms13040862

AMA Style

Song L, Wang S, Zou H, Yi X, Jia S, Li R, Song J. Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development. Microorganisms. 2025; 13(4):862. https://doi.org/10.3390/microorganisms13040862

Chicago/Turabian Style

Song, Lingyun, Sha Wang, Hang Zou, Xiaokang Yi, Shihan Jia, Rongpeng Li, and Jinxing Song. 2025. "Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development" Microorganisms 13, no. 4: 862. https://doi.org/10.3390/microorganisms13040862

APA Style

Song, L., Wang, S., Zou, H., Yi, X., Jia, S., Li, R., & Song, J. (2025). Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development. Microorganisms, 13(4), 862. https://doi.org/10.3390/microorganisms13040862

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