PRODUCTION OF INDOLE ALKALOIDS FROM CATHARANTHUS ROSEUS CELL CULTURES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。玫瑰花植物是重要的抗肿瘤化合物长春新碱和长春碱的来源，长春新碱和长春碱用于治疗白血病、霍奇金病和某些淋巴瘤，还有抗高血压化合物ajmalineine和蛇纹石。这种植物含有极低浓度的这些生物碱化合物（按重量计为0.0005%-0.3%），导致它们的价格很高。此外，从植物中产生这些化合物是不一致的，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、前体和资源的通量。她的目标是开发一种经济上可行的方法，利用植物细胞培养来满足重要的植物衍生药物的需求。研究方法是研究细胞内次生代谢物产生增加的潜在机制，并合理操纵外部条件，使细胞内发生理想的变化。根据其分子量和报道的串联质谱，或将提交样品的光谱与标准样品的光谱进行比较，可以在馏分中识别出一些已知的生化途径中的化合物。互补合作项目探索生物碱在qTOF和FTMS仪器上的碎片化途径。

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.