PRODUCTION OF THE ANTIMALARIAL ARTEMISININ FROM ROOTS

从根中提取抗疟药青蒿素

• 批准号: 2076274
• 负责人: PAMELA J WEATHERS
• 金额: $ 15.15万
• 依托单位: WORCESTER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2076274
• 关键词: antimalarial agents; biotechnology; drug design /synthesis /production; mass tissue /cell culture; plant extracts; terpenes

Malaria currently affects one half of the world's population with an estimated 100-200 million cases and about 1 million deaths annually. Incidence of the disease is increasing due to drug resistance of Plasmodium falciparum. A promising therapeutic, artemisinin, is a terpenoid found at low levels (1% or less) in the herb, Artemisia annua. In tissue cultured plants it occurs at even lower levels. Higher production levels, in either native plants or their cultured tissues, could make therapeutic use of artemisinin and its derivatives feasible on a large scale. Our long-range goal is to complete the bench-scale process studies needed for pilot- scale demonstration of production of artemisinin from transformed Artemisia roots. This work is divided into 4 major objectives to be accomplished over 3 years: 1.) 0ptimize culture conditions to maximize biomass and artemisinin (and related compounds) productivity. Factors to be optimized include culture nutrients (e.g. phosphate, nitrogen, sugar, CO2 etc.), environmental parameters (light, pH, temperature, etc.), and other factors (phytohormones, inoculum age, elicitors etc.) using methods of fractional factorial experimental design. 2.) Minimize artemisinin degradation by peroxidase. Both biomass and artemisinin productivity will be measured and compared with peroxidase activity in the presence of POD inhibitors. 3.) Compare artemisinin recovery processes. Methods using solvents and adsorbents for the nonlethal recovery of artemisinin from root cultures will be studied to maximize product recovery. 4.) Evaluate potential culture systems. Several promising types of bench-scale bioreactors will be used to determine which is most suitable for culture and production of artemisinin from transformed roots using measurements of productivity (g 1-1 day-1). Using the results obtained by these studies, conditions for growth and AN production will be defined. This fundamental information will represent a major advance towards establishing the potential of using root cultures for the production of the antimalarial therapeutic, artemisinin, as well as other plant derived therapeutics.

目前，疟疾影响世界一半的人口 估计每年有1亿例案件和约100万例死亡。 由于耐药性的发病率正在增加 恶性疟原虫。有前途的治疗性阿耳震蛋白是一个 在草药Artemisia Annua中发现的萜类化合物在低水平（1％或更少）中发现。 在组织培养的植物中，它发生在较低水平。更高 在本地植物或其培养的组织中的生产水平， 可以使青蒿素及其衍生物的治疗使用可行 大规模。 我们的远程目标是完成所需的台式过程研究 为了进行试验 - 从 转化的阿耳厄米根源。这项工作分为4个主要目标 要完成3年以上： 1.）0限制培养条件以最大化生物量和青蒿素（和 相关化合物）生产率。要优化的因素包括文化 营养（例如磷酸盐，氮，糖，二氧化碳等），环境 参数（光，pH，温度等）和其他因素 （植物激素，接种年龄，引起者等）使用分数方法 阶乘实验设计。 2.）最大程度地减少过氧化物酶降解的青蒿素降解。生物量和 青蒿素生产率将被测量并与过氧化物酶进行比较 在豆荚抑制剂存在下的活性。 3.）比较青蒿素恢复过程。使用溶剂和 从根培养物中非致命恢复青蒿素的吸附剂 将研究以最大化产品恢复。 4.）评估潜在的培养系统。几种有希望的类型的 台式生物反应器将用于确定哪种最合适的 用于使用转化根的培养和产生青蒿素的培养和生产 生产率的测量（G 1-1天）。 使用这些研究获得的结果，生长条件和 将定义生产。 这些基本信息将 代表建立使用潜力的重大进步 产生抗疟疾治疗的根培养物， 青蒿素以及其他植物衍生的疗法。