Taxol Biosynthesis: Identity of Taxol Direct Precursor in Cell Culture

9632961舒勒，这项拟议研究的目标是鉴定和研究在使用某些代谢抑制剂进行植物组织培养实验时，原理调查员实验室最近发现的一种未知紫杉烷的生物合成意义。这些实验包括培养产生紫杉醇的红豆杉，紫杉醇是一种重要的抗癌新药。目前普遍认为巴卡菌素III是紫杉醇的直接生物合成前体。然而，PI最近的实验表明，巴卡菌素III可以被选择性地完全抑制，而不会对紫杉醇的产生产生任何显著影响。其他抑制实验表明，积累了一种未知的紫杉烷，它不是巴卡菌素III，但实际上可能是紫杉醇的直接前体。这项建议概述了一种多学科的方法来鉴定这种未知的化合物，并利用红豆杉细胞培养对紫杉醇生产的操纵知识和生物合成化学中的成熟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. ***