Continuous bio-separation of lovastatin using a liquid solid circulating fluidized bed ion exchanger

用于从发酵中回收感兴趣的产品的策略涉及几个下游操作，例如过滤以去除细胞或细胞碎片、溶剂提取或离子交换(IEX)以回收和浓缩所需的产品，然后在一个或多个步骤中进行层析和/或结晶以进行最终纯化。发酵可以进行优化，以获得高产量的感兴趣的产品，但一系列下游操作的效率往往很低，运营成本可能很高。本项目的目标是演示一种工业条件下的液固循环流化床(LSCFB)离子交换器(由WESTERN申请专利)。它已经在实验室规模上进行了演示。该系统可用于耦合真菌土曲霉的连续发酵，生产高价值的降胆固醇药物洛伐他汀。安大略省伦敦市的BTR实验室正在使用专有的固态发酵技术生产洛伐他汀。它们需要一种能够处理含有细胞碎片的发酵液的离子交换系统，而LSCFB似乎符合这一标准。与现有商业IEX系统相比，LSCFB流程和设备用于色谱操作的主要优势是其连续、非循环操作和处理未澄清进料的能力。本建议的具体目标是a)将LSCFB耦合到工业相关的发酵液，b)测量较长期LSCFB条件下离子交换介质的磨损，c)改进液体分布器的设计，d)设计适当的控制策略以供PLC实施，以及e)改进树脂选择标准和方法。本次调查的结果将回答有关LSCFB运行的重大技术经济问题，并为可信的运行业绩提供示范。这项技术将立即进入许可和进一步扩大。LSCFB在IEX过程中具有很强的近期应用潜力，例如从发酵生产中回收衣康酸和其他有机酸(柠檬酸、丙酸)、分离乳清蛋白、从食品植物副产品中提取蛋白质、药物残留回收和废水处理。

The strategy used for recovering products of interest from fermentation involves several downstream operations such as filtration to remove cells or cell debris, solvent extraction or ion exchange (IEX) to recover and concentrate the desired product, followed by chromatography and/or crystallization for final purification in one or more steps. Fermentation can be optimized to have products of interest at high yields, but the efficiency of a sequence of downstream operations are often low and operating costs can be high. The goal of this project is to demonstrate a Liquid Solid Circulating Fluidized Bed (LSCFB) Ion Exchanger (patented by Western) under industrial conditions. It has already been demonstrated at lab scale. This system can be used to couple the continuous fermentation of a fungus, Aspergillus terreus, to produce lovastatin, a cholesterol reducing drug of high value. BTR Laboratories, of London, Ontario is manufacturing lovastatin using proprietary solid-state fermentation technology. They require an ion exchange system capable of dealing with broth containing cellular debris, and the LSCFB appears to meet this criterion. The main advantages of the LSCFB process and apparatus over existing commercial IEX systems for chromatographic operations are its continuous, non-cyclic operation and the ability to handle unclarified feeds.    The specific objectives of this proposal are to a) couple the LSCFB to an industrially relevant fermentation broth, b) measure attrition of ion exchange media under longer-term LSCFB conditions, c) refine the design of the liquid distributors, d) design appropriate control strategy for implementation by a PLC, and e) refine resin selection criteria and methods. The results of this investigation will answer significant technoeconomic questions about LSCFB operation, and provide a demonstration of credible operating performance. The technology will move immediately into licensing and further scale-up. The LSCFB has a strong potential for near-term application to IEX processes such as recovery of itaconic acid and other organic acids (citric, propionic) from fermentation production, whey protein isolates, proteins from food plant byproducts, drug residue recovery and wastewater treatment.