实现基本抗癌药物依托泊苷和天尼泊苷在酵母中的可持续供应

实现基本抗癌药物依托泊苷和天尼泊苷在酵母中的可持续供应

作者： 小柯机器人 发布时间：2026/8/3 13:34:03

本期文章：《科学》：Volume 393 Issue 6810

实现基本抗癌药物依托泊苷和天尼泊苷在酵母中的可持续供应，这一成果由首都医科大学 胡雅婷团队经过不懈努力而取得。2026年7月30日出版的《科学》杂志发表了这一最新研究成果。

在这项研究中，课题组建立了一种化学酶途径，通过生物合成前体4′-脱甲基-鬼臼毒素-4-O-葡萄糖苷的单一化学步骤简化了依托泊苷和替尼泊苷的合成，从而实现了这些基本药物的安全供应链。

研究人员表示，木脂素构成了具有治疗潜力的多种植物代谢物家族。其中，木酚毒素型芳四烯木脂素是依托泊苷和天尼泊苷的前体。依托泊苷是一种重要的抗癌药物，被批准用于小细胞肺癌的一线治疗，而替尼泊苷主要用于治疗白血病和一些脑肿瘤。目前，这些药物依赖于从濒危植物六脚木犀草中提取前体，然后进行化学转化。通过鉴定关键的糖基转移酶，并对涉及45种异源酶的60多个基因进行编辑，在酵母中重建了鬼臼毒素型木脂素复杂的生物合成途径。

附：英文原文

Title: Enabling sustainable supply of the essential cancer medicines etoposide and teniposide in yeast

Author: Siyu Shen, Xue Hu, Dan Li, Yuru Tong, Yunpeng Lv, Zhenjiang Tian, Jiadian Wang, Hao Tang, Yapeng Wang, Lan Kang, Jens Nielsen, Luqi Huang, Yating Hu

Issue&Volume: 2026-07-30

Abstract: Lignans constitute a diverse family of plant metabolites with therapeutic potential. Among them, podophyllotoxin-type aryltetralin lignans serve as precursors for etoposide and teniposide. Etoposide is an essential anticancer medicine approved for first-line treatment of small cell lung cancer, whereas teniposide is used for treatment of leukemia and some brain tumors. Currently, these drugs depend on extraction of precursors from the endangered plant Sinopodophyllum hexandrum, followed by chemical transformations. By identifying key glycosyltransferases and executing more than 60 genetic edits involving 45 heterologous enzymes, the complex biosynthetic pathway of podophyllotoxin-type lignans was reconstructed in yeast. In this study, we established a chemoenzymatic route that streamlines the synthesis of etoposide and teniposide through a single chemical step from biosynthetic precursor 4′-demethyl-epipodophyllotoxin-4-O-glucoside, which enables a secure supply chain of these essential medicines.

DOI: aef5438

Source: https://www.science.org/doi/10.1126/science.aef5438

主题：依托泊苷和天尼泊苷