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.

紫杉醇是最早从太平洋紫杉中分离出来的一种强大的植物抗癌药。尽管紫杉醇在临床上取得了许多成功，但紫杉醇用于临床试验的途径有限仍被认为是最重要的挑战。因此，研究人员正在不断尝试寻找创新的方法来满足社区对这种药物的需求。第一步，识别紫杉醇供应的替代来源，例如紫杉属，其他植物属和内生真菌。在下一步中，紫杉醇或相关代谢产物的生物合成途径在原始生物中被操纵，或被引入异源系统，然后在它们中被操纵。在这里，一系列代谢控制方法已经成功开发用于将代谢通量重定向到紫杉醇，包括启动子工程，酶工程，过表达瓶颈酶，转录因子的过高或下调，隐秘基因的激活，消除/最小化竞争途径的通量，可调节的代谢途径，并增加前体的供应。在这篇综述中，我们讨论了关于替代紫杉酚来源及其代谢操纵的研究进展，并提出了近期的挑战和未来的观点。