PRODUCTION OF INDOLE ALKALOIDS FROM CATHARANTHUS ROSEUS CELL CULTURES

从长春花细胞培养物中生产吲哚生物碱

• 批准号: 7369253
• 负责人: CAROLYN W T LEE-PARSONS
• 金额: $ 0.05万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369253
• 关键词: PRODUCTION; INDOLE; ALKALOIDS; CATHARANTHUS; ROSEUS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Catharanthus roseus plant is the source of the important antitumor compounds, vincristine and vinblastine, used in the treatment of leukemia, Hodgkin's disease, and certain lymphomas, and the antihypertensive compounds, ajmalicine and serpentine. The plant contains extremely low concentrations of these alkaloid compounds (0.0005%-0.3% by weight), resulting in their high prices. Moreover, production of these compounds from the plant is inconsistent, being sensitive to changes in the environment. In order to overcome these limitations, Prof. Lee is investigating how the various production-enhancing strategies alter the flux of nutrients, precursors, and resources in the primary and secondary metabolic pathways. Her goal is to develop an economically viable process using plant cell culture to meet the needs and demands of important plant-derived pharmaceuticals. The research approach is to investigate the underlying mechanism by which secondary metabolite production is increased inside the cell and to rationally manipulate the external conditions to cause desirable changes inside the cell. Some compounds known to be in the biochemical pathway could be identified in the fractions, on the basis of their molecular weights and reported tandem MS, or comparison of the spectra obtained for the submitted samples with those of standards. The complementary collaborative project explores fragmentation pathways of the alkaloids on the qTOF and FTMS instruments.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。长春花植物是重要的抗肿瘤化合物长春新碱和长春碱的来源，用于治疗白血病、霍奇金病和某些淋巴瘤，以及抗高血压化合物阿马里辛和蛇纹石。该植物含有极低浓度的这些生物碱化合物（0.0005%-0.3%重量），导致其价格高昂。此外，这些化合物从植物的生产是不一致的，对环境的变化很敏感。为了克服这些限制，李教授正在研究各种提高产量的策略如何改变初级和次级代谢途径中营养物质，前体和资源的流量。她的目标是利用植物细胞培养开发一种经济上可行的工艺，以满足重要植物源药物的需求。研究方法是研究细胞内次级代谢产物产生增加的潜在机制，并合理地操纵外部条件，使细胞内发生所需的变化。根据其分子量和报告的串联MS，或将提交样品的光谱与标准品的光谱进行比较，可以在馏分中鉴别出某些已知存在于生化途径中的化合物。互补的合作项目探讨了生物碱在qTOF和FTMS仪器上的裂解途径。