目的 研究藥用植物梔子Gardenia jasminoides內(nèi)生球毛殼菌Chaetomium globosum HL-3菌株的次級代謝產(chǎn)物及其抗菌活性。方法 運用ITS序列分析與形態(tài)學(xué)對菌株進行鑒定;經(jīng)大米固體發(fā)酵及醋酸乙酯提取后,采用多種色譜技術(shù)(硅膠柱、Sephadex LH-20凝膠柱、反相C₁₈柱)分離純化代謝產(chǎn)物;通過NMR和EI-MS解析化合物結(jié)構(gòu);采用微量稀釋法評價化合物對枯草芽孢桿菌、金黃色葡萄球菌、大腸桿菌及白色念珠菌的抗菌活性。結(jié)果 從菌株HL-3中共分離鑒定出14個化合物,包括9個甾體: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個螺甾烷苷:dispolongioside B(10);1個細(xì)胞松弛素:chaetoglobosin F(11);1個脂肪酸:deepoxyalchornoic acid(12);2個酚類化合物:N-乙?；野?13)、對羥基苯甲醛(14)。活性評價顯示,化合物1～3對革蘭陽性病原菌(枯草芽孢桿菌、金黃色葡萄球菌)具有選擇性抑制活性,最小抑菌濃度(minimal inhibitory concentration,MIC)值范圍為8～64 μg/mL。結(jié)論 系統(tǒng)揭示了梔子內(nèi)生球毛殼菌HL-3的次級代謝產(chǎn)物組成?；衔?b>2、3、5、8～10、12、13為首次從球毛殼菌屬C. globosum中分離獲得。化合物3對枯草芽孢桿菌的活性尤為顯著(MIC為8 μg/mL)。該研究不僅豐富了球毛殼菌屬次級代謝產(chǎn)物的化學(xué)多樣性,也證實了藥用植物梔子內(nèi)生真菌是發(fā)掘具有抗菌活性天然產(chǎn)物的潛在資源,為抗菌藥物先導(dǎo)化合物的發(fā)現(xiàn)提供了參考依據(jù)。

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.

R284.1

國家自然科學(xué)基金資助項目（82160799）；昆明醫(yī)科大學(xué)創(chuàng)新團隊（2024XKTDPY11）；云南省本科教育教學(xué)改革研究項目（JG2023001）；云南省基礎(chǔ)研究計劃（202301AU070217）；云南省科技廳-昆明醫(yī)科大學(xué)聯(lián)合專項（202301AY070001-186）；大學(xué)生創(chuàng)新訓(xùn)練項目（S202410678026，202510678022，S202510678071）