Taxol Biosynthesis: Identity of Taxol Direct Precursor in Cell Culture

本研究的目的是鉴定和研究一种未知的紫杉烷的生物合成意义，该紫杉烷是最近在主要研究人员实验室用某些代谢抑制剂进行植物组织培养实验时发现的。这些实验涉及红豆杉种的培养，这些红豆杉种可以产生一种重要的新型抗癌药物紫杉醇。目前普遍认为，baccatin III是紫杉醇的直接生物合成前体。然而，PI最近的实验表明，baccatin III可以被选择性地完全抑制，而对紫杉醇的生产没有显著影响。其他的抑制实验显示了一种未知的紫杉烷的积累，它不是baccatin III，但实际上它可能是紫杉醇的直接前体。本提案概述了一种多学科方法来鉴定这种未知化合物，并利用红豆杉细胞培养操作紫杉醇生产的知识和生物合成化学中的既定技术来研究其生物合成意义。＊＊＊

9632961 Shuler The goal of this proposed research is to identify and investigate the biosynthetic significance of an unknown taxane recently discovered in the Principle Investigators laboratory while performing plant tissue culture experiments with certain metabolic inhibitors. These experiments involved the culture of Taxus species which produce Taxol, an important new anti-cancer drug. It is currently generally accepted that baccatin III is the direct biosynthetic precursor of Taxol. However, recent experiments by the PI indicate that baccatin III could be selectively and completely inhibited without any significant effect on Taxol production. Other inhibition experiments have shown the accumulation of a single unknown taxane, which is not baccatin III, but which could,, in fact, be the direct precursor of Taxol. This proposal outlines a multidisciplinary approach to identify this unknown compound and investigate its biosynthetic significance using knowledge of manipulation of Taxol production by Taxus cell cultures, and established techniques in biosynthetic chemistry. ***