Coombe-Tennant Toby, Zhu Xiaoping, Wu Shihua, Loake Gary J
Institute of Molecular Plant Sciences, School of Biological Sciences, University of Edinburgh, The King's Buildings, Edinburgh EH9 3BF, UK.
Research Center of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
J Exp Bot. 2025 Jan 1;76(1):124-133. doi: 10.1093/jxb/erae240.
Paclitaxel (PTX) is a high value plant natural product derived from Taxus (yew) species. This plant specialized metabolite (PSM) and its derivatives constitute a cornerstone for the treatment of an increasing variety of cancers. New applications for PTX also continue to emerge, further promoting demand for this WHO-designated essential medicine. Here we review recent advances in our understanding of PTX biosynthesis and its cognate regulation, which have been enabled by the development of transcriptomic approaches and the recent sequencing and annotation of three Taxus genomes. Collectively, this has resulted in the elucidation of two functional gene sets for PTX biosynthesis, unlocking new potential for the use of heterologous hosts to produce PTX. Knowledge of the PTX pathway also provides a valuable resource for understanding the regulation of this key PSM. Epigenetic regulation of PSM in plant cell culture is a major concern for PTX production, given the loss of PSM production in long-term cell cultures. Recent developments aim to design tools for manipulating epigenetic regulation, potentially providing a means to reverse the silencing of PSM caused by DNA methylation. Exciting times clearly lie ahead for our understanding of this key PSM and improving its production potential.
紫杉醇（PTX）是一种从红豆杉属植物中提取的高价值植物天然产物。这种植物特殊代谢产物（PSM）及其衍生物构成了治疗越来越多癌症的基石。PTX的新应用也不断涌现，进一步推动了对这种世界卫生组织指定的基本药物的需求。在此，我们综述了近期在理解PTX生物合成及其相关调控方面取得的进展，这得益于转录组学方法的发展以及最近对三个红豆杉基因组的测序和注释。总体而言，这导致了对PTX生物合成的两个功能基因集的阐明，为利用异源宿主生产PTX开辟了新的潜力。PTX途径的知识也为理解这种关键PSM的调控提供了宝贵资源。鉴于长期细胞培养中PSM产量的损失，植物细胞培养中PSM的表观遗传调控是PTX生产的一个主要问题。最近的进展旨在设计用于操纵表观遗传调控的工具，这可能提供一种手段来逆转由DNA甲基化引起的PSM沉默。显然，对于我们理解这种关键PSM并提高其生产潜力而言，激动人心的时刻即将到来。
