Continuous Production of Alkaloids from Immobilized Catharanthus Roseus

尽管从长春花中获得的吲哚生物碱 ajmalicine 在美国并不是一种重要产品，但它可以作为开发“使能技术”的有用模型，以有效生产潜在的更重要的化合物，例如紫杉醇。 先前的研究表明，结合四种治疗策略可以使 ajmalicine 的细胞外产量增加 50 倍。 这四种策略是：（1）启发； (2)生产介质开发； (3)海藻酸钙固定化； (4)XAD-7树脂原位吸附。 它们协同相互作用，并在间歇式反应器中完成。 重复分批种植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）哪些因素导致长时间培养过程中生产力的损失和细胞生理学的改变； (2) 使用四种组合策略进行连续高水平生产是否可能？

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?