Continuous Production of Alkaloids from Immobilized Catharanthus Roseus

虽然从Catharanthus roseus中提取的吲哚生物碱ajmalicine在美国并不是一种重要的产品，但它为开发一种“使能技术”提供了一个有用的模型，这种技术可以有效地生产潜在的更重要的化合物，如紫杉醇。先前的研究表明，将四种治疗策略结合起来可以使细胞外产生的ajmalineine增加50倍。这四种策略是：(1)启发式；(2)生产介质开发；(3)海藻酸钙固定化；(4) XAD-7树脂原位吸附。它们协同作用，并在间歇式反应器中完成。反复分批栽培的尝试揭示了维持高水平生产的困难。这项工作旨在回答以下问题：(1)在长时间培养过程中，什么因素导致生产力丧失和细胞生理改变；(2)联合使用四种策略是否可能实现持续的高水平生产？

Although the indole alkaloid ajmalicine, obtained from Catharanthus roseus, is not an important product in the U.S., it serves as a useful model for the development of an "enabling technology" for the efficient production of potentially more important compounds, such as taxol. Previous work has shown that combining four treatment strategies can result in a 50-fold increase in the extracellular production of ajmalicine. These four strategies are: (1) elicitation; (2) production medium development; (3) calcium alginate immobilization; and (4) in situ adsorption with XAD-7 resin. They interacted synergistically, and were accomplished in batch reactors. Attempts with repeated batch cultivation revealed difficulties in sustaining a high level of production. This work seeks to answer the following questions: (1) what factors cause the loss of productivity and alterations in cell physiology during prolonged culture; and (2) is continuous high-level production using the combined four strategies possible?