Soliman Sameh, Tang Yi
Departments of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, Los Angeles, California, 90095.
Biotechnol Bioeng. 2015 Feb;112(2):229-35. doi: 10.1002/bit.25468. Epub 2014 Oct 21.
Taxadiene synthase (TXS) is the rate-limiting enzyme in the biosynthesis of paclitaxel, an important anticancer compound. TXS catalyzes the conversion of the diterpene precursor geranylgeranyl pyrophosphate (GGPP) into the diterpene taxadiene. Due to the importance of taxadiene in the overall biosynthetic pathway of paclitaxel biosynthesis, the enzyme TXS has been the subject of intense scientific and engineering investigations. The crystal structure of TXS was recently elucidated, thereby providing an atomic blueprint for future protein engineering efforts. Metabolic engineering of TXS for taxadiene product in different microbial and plant organisms have also been extensively performed, culminating in the high-titer production in Escherichia coli. Additional aspects of taxadiene production by TXS will be discussed in the review, including metabolic regulation in native host and possible production by endophytic fungal hosts.
紫杉二烯合酶（TXS）是重要抗癌化合物紫杉醇生物合成中的限速酶。TXS催化二萜前体香叶基香叶基焦磷酸（GGPP）转化为二萜紫杉二烯。由于紫杉二烯在紫杉醇生物合成的整个生物合成途径中具有重要性，TXS酶一直是深入的科学和工程研究的对象。TXS的晶体结构最近已被阐明，从而为未来的蛋白质工程工作提供了原子蓝图。针对不同微生物和植物生物体中紫杉二烯产物的TXS代谢工程也已广泛开展，最终在大肠杆菌中实现了高滴度生产。本文综述将讨论TXS产生紫杉二烯的其他方面，包括天然宿主中的代谢调控以及内生真菌宿主可能的生产情况。
