Taxol Biosynthesis: Identity of Taxol Direct Precursor in Cell Culture

这项拟议研究的目标是确定和研究一个未知的紫杉烷的生物合成意义，最近发现在主要研究者实验室，同时进行植物组织培养实验与某些代谢抑制剂。 这些实验包括培养能产生紫杉醇（一种重要的新型抗癌药物）的红豆杉属物种。 目前普遍认为浆果赤霉素III是紫杉醇的直接生物合成前体。 然而，PI最近的实验表明，浆果赤霉素III可以被选择性地完全抑制，而对紫杉醇的生产没有任何显着影响。 其他抑制实验显示了一种未知紫杉烷的积累，它不是浆果赤霉素III，但实际上可能是紫杉醇的直接前体。 该提案概述了一个多学科的方法来确定这种未知的化合物，并调查其生物合成的意义，使用知识的操作紫杉醇生产的红豆杉细胞培养物，并建立在生物合成化学技术。 ***

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. ***