Enfumafungin is a natural product derived from fungi, belonging to the triterpene glycoside antibiotic class, and possesses significant antifungal activity[1]. Enfumafungin specifically inhibits 1,3-β-D-glucan synthase, an enzyme essential for fungal cell wall synthesis, thereby disrupting cell wall integrity and leading to fungal death [2]. Enfumafungin can be used to treat systemic infections caused by pathogenic fungi such as Candida and Aspergillus species[3]. Enfumafungin derivatives also demonstrate good activity against azole-resistant fungi, providing lead compounds for the development of new antifungal agents[4].
In vitro, treatment of Candida albicans MY1055 cells with Enfumafungin (0.2–0.5μg/ml) for 4 hours significantly inhibited β-(1,3)-glucan synthase activity, leading to the disruption of cell wall integrity and morphological changes, resulting in cell swelling, aggregate formation, and abnormal branching structures[5].
In vivo, intraperitoneal administration of Enfumafungin (90–162mg/kg) twice daily for two days to immunosuppressed mice with systemic Candida albicans infection significantly reduced the fungal load in the kidneys (ED90=90mg/kg, ED99=162mg/kg). This effect was mediated by the specific inhibition of fungal cell wall β-(1,3)-glucan synthase activity, leading to abnormal fungal cell morphology and death[6].
References:
[1] Kuhnert E, Li Y, Lan N, et al. Enfumafungin synthase represents a novel lineage of fungal triterpene cyclases. Environ Microbiol. 2018 Sep;20(9):3325-3342.
[2] Cao ZQ, Wang GQ, Luo R, et al. Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage. J Am Chem Soc. 2024 May 8;146(18):12723-12733.
[3] Jiménez-Ortigosa C, Paderu P, Motyl MR, et al. Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida Species and Aspergillus species isolates. Antimicrob Agents Chemother. 2014;58(2):1248-51.
[4] Cheng Z, Wu W, Liu Y, et al. Natural Enfumafungin Analogues from Hormonema carpetanum and Their Antifungal Activities. J Nat Prod. 2023 Oct 27;86(10):2407-2413.
[5] Onishi J, Meinz M, Thompson J, et al. Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000 Feb;44(2):368-77.
[6] Peláez F, Cabello A, Platas G, et al. The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms. Syst Appl Microbiol. 2000 Oct;23(3):333-43.
Enfumafungin是一种来源于真菌的天然产物，属于三萜类糖苷抗生素，具有显著的抗真菌活性[1]。Enfumafungin可特异性抑制真菌细胞壁合成所必需的1,3-β-D-葡聚糖合成酶，从而破坏细胞壁完整性导致真菌死亡[2]。Enfumafungin可用于治疗由念珠菌和曲霉菌等病原真菌引起的系统性感染[3]。Enfumafungin的衍生物对唑类耐药真菌也表现出良好活性，为研发新型抗真菌药物提供了先导化合物[4]。
在体外，Enfumafungin（0.2–0.5μg/ml）处理白色念珠菌MY1055细胞4小时，显著抑制β-(1,3)-葡聚糖合成酶活性，导致细胞壁完整性破坏和形态学改变，促使细胞膨大、聚集体形成及异常分枝结构[5]。
在体内，Enfumafungin（90–162mg/kg）腹腔注射处理免疫抑制小鼠每日两次持续两天，显著降低系统性白色念珠菌感染小鼠肾脏真菌载量（ED90=90mg/kg，ED99=162mg/kg），同时通过特异性抑制真菌细胞壁β-(1,3)-葡聚糖合成酶活性导致真菌细胞形态异常和死亡[6]。