紫杉醇药物中间体的微生物生物合成进展概述

The Advance in the Microbe-derived Paclitaxel Intermediates Using Synthetic Biology

紫衫醇是一种高效、低毒、广谱的属于二萜类生物碱天然抗癌药物,通过抑制微管解聚和稳定微管的作用来抑制有丝分裂,已在临床上广泛使用,市场需求量大。由于其来源红豆杉生长缓慢,含量低,紫衫醇分子复杂,化学全合成虽已完成,但产量低,难以应用于工业生产,半合成方法虽较为成熟,但仍然依赖于红豆杉资源。合成生物学技术已被应用于紫衫醇的合成研究中,本文简要分析了紫杉醇药物中间体在大肠埃希菌和酵母菌工程细胞中异源生物合成途径的组建和代谢调控,概述了该技术的进展及所面临的问题。

Paclitaxel （Taxol） was a natural anticancer drugs of diterpene alkaloid with high efficiency, low toxicity and broad-spectrum, which could inhibit mitosis through inhibiting microtubule depolymerization and consequent stabilization of microtubules during the process of cell division. It had become a wildly used anticancer agent in clinic. The market demand was high. Due to the comlexity of the molecular structure, chemical total synthesis of paclitaxel was low yielded and difficult to apply in industrial production. Semi-synthetic method was relatively mature, but still depends on the resources of taxus, which was slow growed and low content. A new method using synthetic biology technology had become research focus. The construction and regulation of the biosynthetic pathway of paclitaxel intermediates in both Escherichia coli and Saccharomyces cerevisiae were briefly reviewed. In particular, the development and problems were also summarized in this research.