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<p><i>Taxus</i> species naturally produce paclitaxel, a secondary metabolite with potent anticancer properties. However, paclitaxel biosynthesis in <i>Taxus</i> cell suspension culture is often inconsistent due to cellular heterogeneity that affects gene expression across cultures and time. This study examined the impact of cell aggregate size on paclitaxel production in <i>Taxus cuspidata</i> P93AF cultures elicited with methyl jasmonate (MeJA). Cultures with smaller aggregates (~ 500&#xa0;μm) showed higher paclitaxel levels than those with big aggregates (~ 1000&#xa0;μm). Furthermore, we analyzed transcriptomic data, identifying key regulatory pathways likely responsible for enhanced paclitaxel production in smaller aggregates and under elicitation with MeJA. This analysis revealed significant activation of membrane-bound transporters and transcription factors that regulate secondary metabolism, along with the paclitaxel pathway genes under MeJA elicited conditions. Results suggest an adaptive metabolic shift from primary to secondary metabolism to optimize synthesis of paclitaxel and secondary products. This study provides key insights into the global cellular gene regulatory mechanisms likely responsible for enhanced paclitaxel production in response to culture stress, offering potential engineering strategies for optimizing paclitaxel yield and promoting <i>Taxus</i> cell culture a sustainable, large-scale production platform for paclitaxel.</p>

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Transcriptomic analysis of Taxus cell suspension cultures reveals insights to guide engineering strategies for enhanced secondary metabolite production

  • 期刊论文

  • 发表日期：

    2026年6月27日

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  • Md Tahsin Rahi,
  • Rohan A. Patil,
  • Sangram K. Lenka,
  • Elsbeth L. Walker,
  • Susan C. Roberts

摘要

Taxus species naturally produce paclitaxel, a secondary metabolite with potent anticancer properties. However, paclitaxel biosynthesis in Taxus cell suspension culture is often inconsistent due to cellular heterogeneity that affects gene expression across cultures and time. This study examined the impact of cell aggregate size on paclitaxel production in Taxus cuspidata P93AF cultures elicited with methyl jasmonate (MeJA). Cultures with smaller aggregates (~ 500 μm) showed higher paclitaxel levels than those with big aggregates (~ 1000 μm). Furthermore, we analyzed transcriptomic data, identifying key regulatory pathways likely responsible for enhanced paclitaxel production in smaller aggregates and under elicitation with MeJA. This analysis revealed significant activation of membrane-bound transporters and transcription factors that regulate secondary metabolism, along with the paclitaxel pathway genes under MeJA elicited conditions. Results suggest an adaptive metabolic shift from primary to secondary metabolism to optimize synthesis of paclitaxel and secondary products. This study provides key insights into the global cellular gene regulatory mechanisms likely responsible for enhanced paclitaxel production in response to culture stress, offering potential engineering strategies for optimizing paclitaxel yield and promoting Taxus cell culture a sustainable, large-scale production platform for paclitaxel.