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

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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.