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<p>Taxol (paclitaxel) is a widely used anticancer drug with a complex biosynthetic pathway that has puzzled biochemists for decades. The endophytic fungus <i>Fusarium tricinctum</i> T6 isolated from the bark of <i>Taxus baccata</i> comprises potential anticancer and antioxidant activities. In the present study, the fungal extract profiling using the UHPLC-ESI-MS/MS technique confirmed the Taxol production from <i>F. tricinctum</i> T6 strain. The study further addressed the long-standing challenge of uncovering the fungal Taxol biosynthesis genes and pathway. In genome-wide sequence analysis, among 13,249 predicted gene models, 8 associated with the mevalonate pathway and 19 other Taxol biosynthesis genes were determined, whereas no single 2-C-methyl-D-erythritol 4-phosphate pathway-related gene was found. The identified fungal Taxol biosynthesis genes are mainly homologous to those in <i>Taxus</i> and other plant species, with low percentage identities. Contrary to past studies, the conserved “DXDD” motif was observed in predicted taxa-4(5),11(12)-diene synthase of <i>F. tricinctum</i> and <i>Pestalotiopsis microspora.</i> Notably, despite the low sequence identities between <i>F. tricinctum</i> and <i>Taxus brevifolia</i> taxa-4(5),11(12)-diene synthase, the remarkable structural similarity of their active sites indicates likely conservation of enzymatic function. The study revealed the Taxol production and sole involvement of the mevalonate pathway in the biosynthesis of Taxol precursors, while supporting the potential independent origin of the Taxol biosynthesis pathway in <i>F. tricinctum</i> from the host plants. This work also provides an understanding of Taxol biosynthesis and establishes a foundation for its biotechnological production.</p>

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Taxol production and Elucidation of its biosynthetic pathway in endophytic fungus Fusarium tricinctum associated with Taxus baccata

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Eetika Chot,
  • M. Vasundhara,
  • Krishna Mohan Medicherla,
  • M. Sudhakara Reddy

摘要

Taxol (paclitaxel) is a widely used anticancer drug with a complex biosynthetic pathway that has puzzled biochemists for decades. The endophytic fungus Fusarium tricinctum T6 isolated from the bark of Taxus baccata comprises potential anticancer and antioxidant activities. In the present study, the fungal extract profiling using the UHPLC-ESI-MS/MS technique confirmed the Taxol production from F. tricinctum T6 strain. The study further addressed the long-standing challenge of uncovering the fungal Taxol biosynthesis genes and pathway. In genome-wide sequence analysis, among 13,249 predicted gene models, 8 associated with the mevalonate pathway and 19 other Taxol biosynthesis genes were determined, whereas no single 2-C-methyl-D-erythritol 4-phosphate pathway-related gene was found. The identified fungal Taxol biosynthesis genes are mainly homologous to those in Taxus and other plant species, with low percentage identities. Contrary to past studies, the conserved “DXDD” motif was observed in predicted taxa-4(5),11(12)-diene synthase of F. tricinctum and Pestalotiopsis microspora. Notably, despite the low sequence identities between F. tricinctum and Taxus brevifolia taxa-4(5),11(12)-diene synthase, the remarkable structural similarity of their active sites indicates likely conservation of enzymatic function. The study revealed the Taxol production and sole involvement of the mevalonate pathway in the biosynthesis of Taxol precursors, while supporting the potential independent origin of the Taxol biosynthesis pathway in F. tricinctum from the host plants. This work also provides an understanding of Taxol biosynthesis and establishes a foundation for its biotechnological production.