内生真菌紫杉醇生物合成的研究现状与展望

Advances and prospects of taxol biosynthesis by endophytic fungi

摘要:

紫杉醇是重要的抗癌药物之一，已经证明其对多种癌症具有显著疗效。目前，人们主要是从红豆杉的树皮中提取、分离和纯化紫杉醇，但由于红豆杉为生长缓慢、散生、濒危的珍稀植物，且随着紫杉醇临床用途的不断拓宽，市场需求的稳定增长，单纯依靠从红豆杉树皮中提取紫杉醇已经无法满足日益增长的市场需求。为了解决紫杉醇的药源不足，科学家已把目光从红豆杉树分离提取紫杉醇转向了其他替代方法，如化学全合成、半合成、组织培养与细胞培养、微生物发酵法生产紫杉醇等。因此，了解内生真菌紫杉醇生物合成的分子基础和遗传调控机制，对解析内生真菌紫杉醇生物合成机制、构建高产紫杉醇基因工程菌株和早日实现内生真菌紫杉醇工业化生产具有重要的科学意义和现实意义。结合本课题组多年来的科研工作，概述了红豆杉细胞紫杉醇生物合成途径、内生真菌发酵生产紫杉醇的优势、产紫杉醇内生菌的分离研究现状和生物多样性及紫杉醇生物合成相关基因的研究现状。内生真菌生物发酵合成紫杉醇是可以无限生产、大量获取紫杉醇、解决紫杉醇药源短缺问题的很有前景的方法之一。

Abstract:

Taxol is one of the most important chemotherapeutic drugs against cancer. Taxol has been mainly extracted from the bark of yews for a long time. However, methods for the extraction of taxol from the bark of Taxus species were inefficient and environmentally costly. As a result of the high ecological toll exacted on trees with the potential for Pacific yew extinction, investigators began to look for other methods of taxol production. Recently, increasing efforts have been made to develop alternative means of taxol production, such as using complete chemical synthesis, semi-synthesis, Taxus spp. plant cell culture and microbe fermentation. Using microbe fermentation in the production of taxol would be a very prospective method for obtaining a large amount of taxol. Therefore, it is necessary to understand the molecular basis and genetic regulation mechanisms of taxol biosynthesis by endophytic fungi, which may be helpful to construct the genetic engineering strain with high taxol output. In this paper, the taxol biosynthesis pathway from Taxus cells and the advantages of taxol biosynthesis by endophytic fungi were discussed. The study on the isolation and biodiversity of taxol-producing endophytic fungi and the taxol biosynthesis related genes are also discussed.