Abstract：
Paclitaxel (PTX) is a high value plant natural product (PNP) derived from Taxus (yew) species. This plant secondary 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 (PCC) 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.
摘要：
紫杉醇（PTX）是一种高价值的植物自然产品（PNP），来源于紫杉（紫杉）物种。这种植物次级代谢物(PSM)及其衍生物构成了治疗越来越多的癌症的基石。PTX的新应用也不断涌现，进一步促进对这一世卫组织指定基本药物的需求。在这里，我们回顾了我们对PTX生物合成及其同源调控的理解的最新进展，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。总的来说，这导致了PTX生物合成的两个功能基因集的阐明，释放使用异源宿主生产PTX的新潜力。PTX途径的知识也为理解该关键PSM的调节提供了宝贵的资源。植物细胞培养（PCC）中PSM的表观遗传调控是PTX生产的主要关注点，考虑到长期细胞培养中PSM产量的损失。最近的发展旨在设计用于操纵表观遗传调控的工具，可能提供一种逆转由DNA甲基化引起的PSM沉默的方法。对于我们对这一关键PSM的理解和提高其生产潜力来说，令人兴奋的时刻显然还在前面。
