Fernie Alisdair R, Liu Fang, Zhang Youjun
Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany.
Key Laboratory of Seed Innovation, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Nat Plants. 2024 Dec;10(12):1875-1885. doi: 10.1038/s41477-024-01869-8. Epub 2024 Nov 27.
Paclitaxel rapidly became one of the most effective anticancer drugs. However, the production of paclitaxel is hindered by substantial challenges, particularly considering the significant quantities of drug required and the inherently low concentration of paclitaxel and its intermediates in plants. Paclitaxel is currently produced in a so-called semi-synthesis in which baccatin III is extracted from Taxus species and chemically converted to paclitaxel. Despite the fact that many of the intermediates of paclitaxel biosynthesis are yet to be experimentally determined, a set of recent papers-facilitated by the sequencing and assembly of three Taxus genomes-has uncovered the minimal gene sets for both baccatin III and paclitaxel biosynthesis. Here we summarize the key milestones towards our understanding of paclitaxel biosynthesis and highlight recent advancements made possible by genome-level analysis of potential key genes involved. We argue that these studies will ultimately pave the way towards the elucidation of the entire paclitaxel biosynthetic pathway and facilitate the industrial production of paclitaxel via synthetic biology approaches. However, several major challenges lie ahead before we can fully tap into the amazing curative potential that taxanes provide.
紫杉醇迅速成为最有效的抗癌药物之一。然而，紫杉醇的生产面临诸多重大挑战，特别是考虑到所需药物的大量需求以及植物中紫杉醇及其中间体固有的低浓度。目前，紫杉醇是通过所谓的半合成生产的，其中从红豆杉属植物中提取巴卡亭III并将其化学转化为紫杉醇。尽管紫杉醇生物合成的许多中间体尚未通过实验确定，但最近一系列由三个红豆杉基因组的测序和组装推动的论文揭示了巴卡亭III和紫杉醇生物合成的最小基因集。在这里，我们总结了我们对紫杉醇生物合成理解的关键里程碑，并强调了通过对潜在关键基因进行基因组水平分析而取得的最新进展。我们认为，这些研究最终将为阐明整个紫杉醇生物合成途径铺平道路，并通过合成生物学方法促进紫杉醇的工业化生产。然而，在我们能够充分挖掘紫杉烷所具有的惊人治疗潜力之前，仍有几个重大挑战摆在面前。
