紫杉醇
代谢工程
生物
红豆杉
计算生物学
焊剂(冶金)
代谢途径
合成生物学
转录因子
瓶颈
代谢网络
生物技术
生物信息学
计算机科学
酶
基因
癌症
生物化学
化学
遗传学
有机化学
嵌入式系统
植物
作者
Mohammad Sabzehzari,Masoumeh Zeinali,Mohammad Reza Naghavi
标识
DOI:10.1016/j.biotechadv.2020.107569
摘要
Paclitaxel is one of the strong plant-derived anti-cancer drugs that was first isolated from the Pacific yew. Despite many paclitaxel's clinical successes, the limited accessibility of paclitaxel for clinical trials is recognized as the most important challenge. Thus, researchers are continuously trying to find the innovative ways to meet the community's need for this medicine. In the first step, the alternative sources for Taxol supply were recognized, such as Taxus genus, other plant genera, and endophytic fungi. In the next step, the biosynthetic pathways of Taxol or related metabolites were manipulated in the original organisms, or introduced to heterologous systems and then were manipulated in them. Here, a range of metabolic manipulating approaches have been successfully developed to redirect the metabolic flux toward Taxol, including promoter engineering, enzyme engineering, overexpressing the bottleneck enzymes, over- or down-regulation of transcription factors, activation of the cryptic genes, removing/minimizing the flux for competing pathways, tunable regulation of the metabolic pathway, and increasing the supplies of precursors. In this review, we discuss research progress on the alternative Taxol sources and its metabolic manipulating, and we suggest recent challenges and future perspectives.
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