Exploring metabolite diversification via OSMAC strategy and UPLC-QTOF-MS in Aspergillus sp. Y-WS27

IF 2.5 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia Pub Date : 2025-06-05 DOI:10.1016/j.fitote.2025.106665

Ming Chen , Yuting Wu , Peixi Zhang , Zhenxiong Lin , Jiaqi Shi , Jing Li , Bonan Yan , Li Guo , Wenxi Zhang , Qi Shi , Jieqing Liu

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引用次数: 0

Abstract

This study investigated the efficacy of the One Strain Multiple Compounds (OSMAC) strategy in enhancing the anti-cancer potential of metabolites derived from the marine fungus Aspergillus sp. Y-WS27. Twenty-five culture conditions were employed to assess the inhibitory effects of crude extracts on cancer cell proliferation. Among them, the extract obtained from rice solid culture (R-0) demonstrated significantly enhanced inhibitory activity, as revealed by base peak chromatograms (BPC). The metabolite profile of R-0 showed a marked increase in the diversity and abundance of secondary metabolites compared to the control group (P-0). Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), along with ACD/MS Structure ID Suite, identified eight distinct compounds (1–8). These included butyrolactones, terretonins, and monacolin derivatives. Further purification yielded 17 compounds (1–17), with compounds 7 and 9 exhibiting significant anti-proliferative effects against MCF-7, A549, and HeLa cancer cells (IC₅₀ values ranging from 9.88 to 30.28 μg/mL). Compound 7 displayed superior efficacy with IC₅₀ values of 12.12, 10.21, and 9.88 μg/mL, respectively, while compound 9 showed moderate activity with reduced cytotoxicity to normal HK-2 cells. These findings demonstrated the utility of the OSMAC strategy in modulating secondary metabolite production and revealing previously undetected compounds. This research provided a robust framework for the discovery of novel natural products with therapeutic potential against cancer.

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利用OSMAC策略和UPLC-QTOF-MS研究曲霉Y-WS27的代谢物多样性。

本文研究了一株多化合物（OSMAC）策略对海洋真菌Aspergillus sp. Y-WS27代谢产物抗癌潜力的增强作用。采用25种培养条件评价粗提物对癌细胞增殖的抑制作用。其中，基峰色谱（BPC）显示，从水稻固体培养物（R-0）中获得的提取物具有显著增强的抑制活性。代谢产物谱显示，与对照组相比，R-0组次生代谢产物的多样性和丰度显著增加（P-0）。超高效液相色谱联用四极杆飞行时间质谱（UPLC-QTOF-MS），以及ACD/MS结构ID Suite，鉴定出8种不同的化合物（1-8）。这些药物包括丁内酯、地酮素和莫纳可林衍生物。进一步纯化得到17个化合物（1-17），其中化合物7和9对MCF-7、A549和HeLa癌细胞具有显著的抗增殖作用（IC50值为9.88 ~ 30.28 μg/mL）。化合物7的IC50值分别为12.12、10.21和9.88 μg/mL，而化合物9的活性适中，对正常HK-2细胞的毒性降低。这些发现证明了OSMAC策略在调节次生代谢物产生和揭示以前未检测到的化合物方面的效用。这项研究为发现具有抗癌治疗潜力的新型天然产物提供了一个强有力的框架。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fitoterapia 医学-药学

CiteScore

5.80

自引率

2.90%

发文量

198

审稿时长

1.5 months

期刊介绍： Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.