PRODUCTION OF TAXOL BY PLANT TISSUE CULTURE

调查的总体目的是发展一个经济 制备紫杉醇或功能类似化合物的方法， 在生物反应器中使用植物组织培养。 紫杉醇是一种抗肿瘤药物 主要来源于短叶红豆杉，西部紫杉。 它有 对癌症，特别是难治性癌症具有优异的确认活性 人类卵巢癌 t. brevifolia生长非常缓慢， 严重限制了药物的供应。 植物细胞 而组织培养有可能提供一种可控的 满足临床试验和后续需求的药物，如果 批准用于一般临床用途。 拟议的工作旨在发展技术知识库， 这些领域对紫杉醇的经济生物反应器生产至关重要。 关键 研究的领域是选择高紫杉烷生产细胞， 预防紫杉烷代谢，保护细胞免受任何不利的 紫杉烷的作用和减轻任何代谢速率限制步骤。 这项工作将在一个应用框架内完成， 生物工程扩大标准，以确定所需的领域， 改进. 短期内，这项工作将形成一个重要的 组织培养发展独立计划基金会 方案和生物反应器中的放大。 从长远来看， 研究将确定诱导紫杉醇的策略 生物合成和生产力的提高。

The overall purpose of the investigation is to develop an economic process for the production of taxol, or functionally similar compounds, in bioreactors using plant tissue culture. Taxol is an antitumor drug derived primarily from Taxus brevifolia, the Western Yew. It has excellent confirmed activity against cancer, particularly refractory human ovarian cancers. T. brevifolia is very slow growing and sufficiently rate to seriously limit the supply of the drug. Plant cell and tissue culture has the potential to provide a controlled supply of the drug to meet the needs of clinical trials and subsequent demand if approved for general clinical use. The proposed work is intended to develop the knowledge base in technical areas that are critical to economic bioreactor production of taxol. Key areas of the investigation are selection of high taxane producing cells, prevention of taxane catabolism, protection of cells from any adverse effects of taxanes and mitigation of any metabolic rate limiting steps. The work will be completed within an applied framework that uses bioengineering scale-up criteria to determine areas needed for improvement. In the short-term, the work will form an important foundation for independent programs in development of tissue culture protocols and scale-up in bioreactors. In the longer term, the investigations will identify strategies for induction of taxol biosynthesis and productivity improvements.