PRODUCTION OF TAXOL BY PLANT TISSUE CULTURE

调查的总体目的是为了发展一种经济 紫杉醇或功能类似化合物的生产方法， 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，西部红豆杉。它有 出色的抗癌活性，特别是难治性 人类卵巢癌。短叶黄杨生长非常缓慢， 足以严重限制这种药物的供应。植物细胞 而组织培养有可能提供有控制的供应 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。 拟议的工作旨在开发技术领域的知识库 对生物反应器生产紫杉醇经济至关重要的领域。钥匙 调查的领域是选择高产紫杉烷的细胞， 防止紫杉烷分解代谢，保护细胞免受任何不利影响 紫杉烷的影响和任何代谢速率限制步骤的缓解。 工作将在一个应用框架内完成，该框架使用 生物工程放大标准以确定所需的区域 进步。在短期内，这项工作将形成重要的 组织培养发展中的独立项目基础 生物反应器中的协议和放大。从长远来看， 调查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.