目的 研究药用植物栀子Gardenia jasminoides内生球毛壳菌Chaetomium globosum HL-3菌株的次级代谢产物及其抗菌活性。方法 运用ITS序列分析与形态学对菌株进行鉴定;经大米固体发酵及醋酸乙酯提取后,采用多种色谱技术(硅胶柱、Sephadex LH-20凝胶柱、反相C₁₈柱)分离纯化代谢产物;通过NMR和EI-MS解析化合物结构;采用微量稀释法评价化合物对枯草芽孢杆菌、金黄色葡萄球菌、大肠杆菌及白色念珠菌的抗菌活性。结果 从菌株HL-3中共分离鉴定出14个化合物,包括9个甾体:ergosta-5,7,22-trien-3β-ol(1)、5α,8α-epidioxyergosta-6,22-dien-3-ol(2)、3β,5α-dihydroxy-6β-methoxyergosta-7,22-diene(3)、melithasterol B(4)、(3β,5α,8α)-5,8-epidioxyergosta-6,9(11),22-trien-3-ol(5)、谷甾醇(6)、5α,6α-epoxy-ergosta-8,22-diene-3β,7α-diol(7)、stigmasterol-3-O-β-D-glucopyranoside(8)、β-sitosteryl-3-O-β-D-glucopyranoside-20-O-palmitate(9);1个螺甾烷苷:dispolongioside B(10);1个细胞松弛素:chaetoglobosin F(11);1个脂肪酸:deepoxyalchornoic acid(12);2个酚类化合物:N-乙酰基酪胺(13)、对羟基苯甲醛(14)。活性评价显示,化合物1～3对革兰阳性病原菌(枯草芽孢杆菌、金黄色葡萄球菌)具有选择性抑制活性,最小抑菌浓度(minimal inhibitory concentration,MIC)值范围为8～64 μg/mL。结论 系统揭示了栀子内生球毛壳菌HL-3的次级代谢产物组成。化合物2、3、5、8～10、12、13为首次从球毛壳菌属C. globosum中分离获得。化合物3对枯草芽孢杆菌的活性尤为显著(MIC为8 μg/mL)。该研究不仅丰富了球毛壳菌属次级代谢产物的化学多样性,也证实了药用植物栀子内生真菌是发掘具有抗菌活性天然产物的潜在资源,为抗菌药物先导化合物的发现提供了参考依据。

Objective To investigate the secondary metabolites and their antimicrobial activities from the endophytic fungus Chaetomium globosum HL-3, isolated from the medicinal plant Gardenia jasminoides. Methods The HL-3 strain was identified using ITS sequence analysis and morphological characteristics. Secondary metabolites were obtained via rice solid-state fermentation, extracted with ethyl acetate, and purified using various chromatographic techniques (silica gel, Sephadex LH-20, and reversed-phase C₁₈ columns). Compound structures were elucidated by NMR and EI-MS analyses. Antimicrobial activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans were evaluated using the broth microdilution method. Results A total of 14 compounds were isolated and identified from the strain HL-3, including nine steroids: ergosta-5,7,22-trien-3β-ol (1), 5α,8α-epidioxyergosta-6,22-dien-3-ol (2), 3β,5α-dihydroxy-6β-methoxyergosta-7,22-diene (3), melithasterol B (4), (3β,5α,8α)-5,8-epidioxyergosta-6,9(11),22-trien-3-ol (5), sitosterol (6), 5α,6α-epoxy-ergosta-8,22-diene-3β,7α-diol (7), stigmasterol-3-O-β-D-glucopyranoside (8), β-sitosteryl-3-O-β-D-glucopyranoside-20-O-palmitate (9); one spirostane glycoside: dispolongioside B (10); one cytochalasin: chaetoglobosin F (11); one fatty acid: deepoxyalchornoic acid (12); and two phenolic compounds: N-acetyltyramine (13), p-hydroxybenzaldehyde (14). Antimicrobial evaluation revealed that compounds 1—3 exhibited selective inhibitory activity against Gram-positive pathogens (B. subtilis and S. aureus), with MIC values ranging from 8 to 64 μg/mL. Compound 3 showed notably stronger activity against B. subtilis (MIC = 8 μg/mL). Conclusion This study systematically characterized the secondary metabolite profile of the endophytic C. globosum HL-3 from G. jasminoides. Compounds 2, 3, 5, 8—10, 12, and 13 were reported for the first time from the Chaetomium globosum species. The findings suggested that endophytic fungi inhabiting medicinal plants like G. jasminoides represent a potential source for discovering antimicrobial natural products. This research contributes to expanding the known chemical diversity of C. globosum metabolites and provides a reference for identifying potential lead compounds for antimicrobial drug development.

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国家自然科学基金资助项目（82160799）；昆明医科大学创新团队（2024XKTDPY11）；云南省本科教育教学改革研究项目（JG2023001）；云南省基础研究计划（202301AU070217）；云南省科技厅-昆明医科大学联合专项（202301AY070001-186）；大学生创新训练项目（S202410678026，202510678022，S202510678071）