紫杉醇生物合成和调控的最新进展。
Recent advances in paclitaxel biosynthesis and regulation.
发表日期:2024 May 23
作者:
Toby Coombe-Tennant, Xiaoping Zhu, Shihua Wu, Gary J Loake
来源:
Epigenetics & Chromatin
摘要:
紫杉醇 (PTX) 是一种源自红豆杉属的高价值植物天然产物 (PNP)。这种植物次生代谢产物 (PSM) 及其衍生物构成了治疗越来越多癌症的基石。 PTX 的新应用也不断出现,进一步促进了对这一世界卫生组织指定基本药物的需求。在这里,我们回顾了对 PTX 生物合成及其同源调控的理解的最新进展,这些进展是通过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而实现的。总的来说,这导致了 PTX 生物合成的两个功能基因集的阐明,释放了使用异源宿主生产 PTX 的新潜力。 PTX 途径的知识也为理解这一关键 PSM 的调节提供了宝贵的资源。鉴于长期细胞培养中 PSM 产量的损失,植物细胞培养 (PCC) 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操纵表观遗传调控的工具,有可能提供一种逆转 DNA 甲基化引起的 PSM 沉默的方法。对于我们了解这一关键的 PSM 并提高其生产潜力来说,激动人心的时刻显然就在眼前。© 作者 2024。由牛津大学出版社代表实验生物学学会出版。版权所有。如需商业重复使用,请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需更多信息,请联系journals.permissions@oup.com。
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.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.