YIELD OF ARTEMISININ BIOSYNTHESIS IN ARTEMISIA ANNUA

青蒿中青蒿素生物合成的产量

• 批准号: 6140949
• 负责人: MICHAEL S DOBRES
• 金额: $ 11万
• 依托单位: NOVAFLORA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6140949
• 关键词: angiosperms; antimalarial agents; genetic manipulation; genetically modified plants; malaria; medicinal plants; plant proteins; protein biosynthesis; protein engineering; sesquiterpenes

Malaria affects up to 500 million people each year. Most who die are under five years old. We propose to enhance the yield of the anti-malarial compound artemisinin in Artemisia annua. We will uses a novel approach to increase the number of artemisinin producing glands through genetic engineering. Artemisinin, though a highly effective antimalarial compound, is produced in very low quantities by A. annua. The yield is currently too low to allow cost effective production from existing varieties of A. annua. Artemisinin is unique and important among other antimalarial compounds in that no known resistant strains of plasmodium have yet been identified. Alternative, approaches to significantly increase artemisinin yield through tissue culture have so far been unsuccessful. Chemical synthesis of artemisinin is cost prohibitive and too difficult for commercial application. The proposed approach should significantly lower the cost and increase the availability of artemesinin. Furthermore, the approach of increasing medicinal product accumulation through increased formation of the respective plant-product producing glands should be applicable to many other plant derived medicinal compounds. PROPOSED COMMERCIAL APPLICATIONS: This technology will make it possible to produce medically important, complex natural product in plants. Licensing of the technology will open a new are of business to NovaFlora. The potential impact of this technology on drug development is valued in the billions. NovaFlora will be able to develop a new product line and expand from the present focus on ornamental plants into medically relevant plants.

疟疾每年影响多达5亿人。大多数死亡者都在5岁以下。我们建议提高青蒿中抗疟疾化合物青蒿素的产量。我们将使用一种新的方法，通过基因工程增加青蒿素生产腺体的数量。青蒿素虽然是一种高效的抗疟化合物，但由A. annua。目前的产量太低，不能从现有的A. annua。青蒿素在其他抗疟化合物中是独特和重要的，因为尚未发现已知的疟原虫耐药株。通过组织培养显著提高青蒿素产量的替代方法迄今为止尚未成功。青蒿素的化学合成成本高昂，难以商业化应用。拟议的办法应能大大降低青蒿素的成本，增加青蒿素的供应。此外，通过增加相应植物产物产生腺体的形成来增加药物产物积累的方法应该适用于许多其它植物衍生的药物化合物。拟议的商业应用：这项技术将使在植物中生产具有医学重要性的复杂天然产品成为可能。该技术的许可将为NovaFlora开辟一个新的业务领域。这项技术对药物开发的潜在影响价值数十亿美元。NovaFlora将能够开发新的产品线，并从目前的观赏植物扩展到医疗相关植物。