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Research progress in high yielding suspension cell lines and the induction of Taxol in Taxus

WANG Mu-Lan;YANG Sheng-Chao;YU Bu-Zhu;LI Wei-Qi;Yunnan Research Center on Good Agriculture Practice for Dominant Chinese Medicinal Materials,Yunnan Agriculture University;Germplasm Bank of Wild Species,Kunming Institute of Botany,Chinese Academy of Sciences;  
Taxol,a diterpene alkaloid secondary metabolite of Taxus species,has been considered as one of the most promising anticancer drugs used for the treatment of several types of cancer. However,due to the difficulties in obtaining enough this compound from Taxus trees,the traditional approach extracted directly from plants not only produces low yield,but also triggers serious damage to the wild resource of Taxus. At the same time,the complex structure Taxol has impeded efforts to find a method to fulfill an economically feasible strategy via total synthesis. By constrast,cell culture of Taxus is a potential alternative for the production of Taxol and analogue compounds in a large scale culture,which possesses a multitude of advantages such as high purity product of secondary metabolite,low production cost,short cell growth cycle and less influence from external factors. Huge efforts have been made to develop a more sustainable source of Taxol. The main target of ongoing Taxus-related research in recent years are on the regulation of Taxus metabolism,key genes mining,application and development in new pharmaceutical preparations. Different ways,including application of precursors and elicitors,optimizing of cultural conditions,screening of high yielding cell lines,optimization of growth and production media,have been already tested to improve the yield of Taxol in cultures of Taxus. It is necessary to take into account the latest achievements based on empirical procedures to establish a high yielding system. In this review,we have summarized the latest endeavors to establish a high yield suspension cell line and increase its yield of Taxol,with a special focus on the key issues related to tissue culture of Taxus such as explants,culture medium,hormone treatment,culture conditions,browning and other issues. Developments for new and more effective elicitation treatments and the application of metabolic engineering to design new transgenic cell lines of Taxus with an improved capacity for taxane production have also been described. In the end,the article discusses the faultiness of current researches and prospects various combinational methods for raising Taxol content. This paper is helpful for promoting technology progress of tissue culture in Tuaxs and it will provide the guidance for the protection and application of medicinal resources.
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