合成生物学确定了植物底盘中帕克利塔克塞尔生物合成所需的最小基因组
Youjun Zhang1, Lorenz Wiese2, Hao Fang3
1Max-Planck-Institut für Molekulare Pflanzenphysiologie, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria.
Molecular plant
|October 28, 2023
概括
研究人员确定了缺少的帕克利塔克塞尔 (Taxol) 生物合成基因,使其在植物中产生. 这一突破克服了关键癌症药物的供应限制.
科学领域:
- 植物代谢工程是植物代谢工程.
- 自然产品的生物合成.
- 化疗药物开发 化疗药物开发
背景情况:
- 帕克利塔塞尔 (Taxol) 是固体癌症的重要化疗药物.
- 天然帕克利塔克塞尔供应有限,需要使用替代生产方法.
- 对帕克利塔克塞尔生物合成基因的不完全知识阻碍了代谢工程.
研究的目的:
- 为了确定异质帕克利塔塞尔生产的完整基因组.
- 为了阐明帕克利塔克塞尔生物合成途径中缺失的步骤.
- 为了建立一种基于植物的代谢路径,用于脱氧化物合成.
主要方法:
- 综合转录组学,细胞生物学,代谢组学和途径复合.
- 在Nicotiana benthamiana中酶的异质表达.
- 新生物合成酶的识别和功能确认.
主要成果:
- 在帕克利塔塞尔生物合成中确定了缺失的基因和确认的酶活性.
- 发现了一种新的C4β-C20环氧酶,解决了代谢工程的一个关键瓶.
- 在N. benthamiana中成功生物合成了baccatin III并将其转化为paclitaxel.
结论:
- 建立了一个综合的代谢路径,以在异种植物系统中进行体生物合成.
- 提供了对复杂生物活性化合物的植物代谢途径的见解.
- 为可持续和可扩展的帕克利塔克塞尔生产铺平了道路.
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