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在短叶红豆杉的内生真菌中寻找能够产生紫杉醇的微生物。

The search for a taxol-producing microorganism among the endophytic fungi of the Pacific yew, Taxus brevifolia.

作者信息

Stierle A, Strobel G, Stierle D, Grothaus P, Bignami G

机构信息

Department of Plant Pathology, Montana State University, Bozeman 59717, USA.

出版信息

J Nat Prod. 1995 Sep;58(9):1315-24. doi: 10.1021/np50123a002.

Abstract

Endophytic microbes associated with the Pacific yew tree, Taxus brevifolia, were examined as potential sources of the anticancer drug taxol [1], a secondary metabolite of the host organism. The first promising organism found was the novel fungus, Taxomyces andreanae, which was isolated from the inner bark of a yew tree growing in northwestern Montana. It appears to produce taxol and other taxanes in de novo fashion when grown in semi-synthetic liquid media. The presence of 1 in the fungal extract was confirmed by mass spectrometry, comparative chromatographic behavior with "yew" taxol, reactivity with taxol-specific monoclonal antibodies, and 9KB cytotoxicity studies. Both acetate-1-14C and phenylalanine UL-14C served as precursors of taxol-14C in fungal culture labeling studies, confirming the de novo synthesis of 1 by the fungus. Immunoassay techniques are currently being used to screen extracts of Taxomyces andreanae for new taxanes, and to determine if other endophytic fungi are taxol producers.

摘要

与太平洋紫杉(短叶红豆杉)相关的内生微生物被作为抗癌药物紫杉醇[1](宿主生物体的一种次生代谢产物)的潜在来源进行了研究。发现的第一种有前景的生物体是新型真菌安德紫杉菌,它是从生长在蒙大拿州西北部的一棵紫杉树的内皮中分离出来的。当在半合成液体培养基中生长时,它似乎能以从头合成的方式产生紫杉醇和其他紫杉烷。通过质谱分析、与“紫杉”紫杉醇的比较色谱行为、与紫杉醇特异性单克隆抗体的反应性以及9KB细胞毒性研究,证实了真菌提取物中存在1。在真菌培养标记研究中,乙酸盐-1-14C和苯丙氨酸-UL-14C均作为紫杉醇-14C的前体,证实了真菌对1的从头合成。免疫测定技术目前正用于筛选安德紫杉菌的提取物以寻找新的紫杉烷,并确定其他内生真菌是否为紫杉醇生产者。

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