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Exploring metabolite diversification via OSMAC strategy and UPLC-QTOF-MS in Aspergillus sp. Y-WS27
Ming Chen1, Yuting Wu1, Peixi Zhang1
1School of Medicine, Huaqiao University, Quanzhou 362021, China.
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.
Insights
The One Strain Multiple Compounds (OSMAC) strategy boosted anti-cancer compound discovery from marine fungus Aspergillus sp. Y-WS27. This approach identified potent anti-proliferative compounds, including compound 7, effective against various cancer cells.
Area of Science:
- Natural Product Chemistry
- Marine Biotechnology
- Cancer Research
Background:
- Marine fungi are a rich source of bioactive secondary metabolites.
- The One Strain Multiple Compounds (OSMAC) strategy can modulate fungal secondary metabolism.
- Discovering novel anti-cancer agents from natural sources is crucial.
Purpose of the Study:
- To investigate the efficacy of the OSMAC strategy for enhancing anti-cancer metabolite production from Aspergillus sp. Y-WS27.
- To identify and characterize novel anti-cancer compounds from this marine fungus.
- To evaluate the anti-proliferative activity of isolated compounds against human cancer cell lines.
Main Methods:
- Application of the OSMAC strategy with 25 culture conditions.
- Analysis of metabolite profiles using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).
- Structure elucidation using ACD/MS Structure ID Suite and compound purification.
- In vitro anti-proliferative assays against MCF-7, A549, HeLa, and HK-2 cancer cells.
Main Results:
- The rice solid culture (R-0) extract showed significantly enhanced inhibitory activity against cancer cells.
- OSMAC strategy increased the diversity and abundance of secondary metabolites.
- Eight distinct compounds were initially identified, with 17 isolated after purification.
- Compounds 7 and 9 exhibited significant anti-proliferative effects, with compound 7 being particularly potent (IC50: 9.88–12.12 μg/mL).
- Compound 9 showed moderate activity with lower cytotoxicity to normal cells.
Conclusions:
- The OSMAC strategy is effective in modulating secondary metabolite production in marine fungi.
- This approach facilitated the discovery of novel anti-cancer compounds, including potent butyrolactones, terretonins, and monacolin derivatives.
- The identified compounds, especially compound 7, represent promising leads for developing new cancer therapeutics.
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