<p>Endophytic fungi have emerged as significant alternative sources of plant-derived bioactive metabolites, such as flavonoids that exhibit antioxidant, antibacterial, and anticancer activities. This study presents a genome-guided discovery of the biosynthesis and bioactivity of liquiritigenin in the endophytic fungus <i>Fusarium solani</i> R1 isolated from the root tissue of <i>Glycyrrhiza uralensis</i> in China. Whole-genome sequencing produced a 54.3&#xa0;Mb draft genome and identified phenylpropanoid and flavonoid pathway genes, including PAL, 4CL, HCT, DFR, FLS, and β-glucosidase, as well as a T3PKS cluster in antiSMASH Region 10.1, indicating a potential role in aromatic polyketide or flavonoid-like metabolism. Metabolic profiling using high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC–MS) confirmed that <i>F. solani</i> R1 produced a liquiritigenin titer of 25&#xa0;mg/L in the fermentation extract. The crude extract demonstrated strong, concentration-dependent antioxidant activity in both DPPH and phosphomolybdenum assays, which correlated with elevated total flavonoid contents. Additionally, the extract displayed broad-spectrum antibacterial activity and induced significant cytotoxicity in HeLa cervical cancer cells, as evidenced by apoptotic morphological changes. Collectively, these results identify <i>F. solani</i> R1 as a promising microbial source of bioactive flavonoids with potential therapeutic applications.</p> Graphical Abstract <p></p>

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Genome-guided discovery of liquiritigenin biosynthesis and bioactivities in the endophytic fungus Fusarium solani R1

  • Shadab Begum,
  • Xinhong Wu,
  • Mehwish Shah,
  • Nazidi Ibrahim,
  • Yiran Li,
  • Aqsa Kanwal,
  • Shiqi Chen,
  • Luhua Jiang,
  • Yili Liang,
  • Xueduan Liu

摘要

Endophytic fungi have emerged as significant alternative sources of plant-derived bioactive metabolites, such as flavonoids that exhibit antioxidant, antibacterial, and anticancer activities. This study presents a genome-guided discovery of the biosynthesis and bioactivity of liquiritigenin in the endophytic fungus Fusarium solani R1 isolated from the root tissue of Glycyrrhiza uralensis in China. Whole-genome sequencing produced a 54.3 Mb draft genome and identified phenylpropanoid and flavonoid pathway genes, including PAL, 4CL, HCT, DFR, FLS, and β-glucosidase, as well as a T3PKS cluster in antiSMASH Region 10.1, indicating a potential role in aromatic polyketide or flavonoid-like metabolism. Metabolic profiling using high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC–MS) confirmed that F. solani R1 produced a liquiritigenin titer of 25 mg/L in the fermentation extract. The crude extract demonstrated strong, concentration-dependent antioxidant activity in both DPPH and phosphomolybdenum assays, which correlated with elevated total flavonoid contents. Additionally, the extract displayed broad-spectrum antibacterial activity and induced significant cytotoxicity in HeLa cervical cancer cells, as evidenced by apoptotic morphological changes. Collectively, these results identify F. solani R1 as a promising microbial source of bioactive flavonoids with potential therapeutic applications.

Graphical Abstract