Abstract

A new recirculating continuous bioreactor-separator combination system is designed and its practical application demonstrated for continuous production and separation of high-purity product. The process performance data and the production cost were evaluated and compared to those available from the conventional batch or semicontinuous biotransformation processes. The new design concept consists of three main components: a tapered column bioreactor, the crystallizer-separator unit, and the substrate feeding reservoir unit. The operating principles of the new bioreactor system are as follows: (1) the tapered column bioreactor unit could employ immobilized cell or enzyme and could be operated as a fluidized-bed or a packed-bed reactor system; (2) the effluent from the bioreactor is transferred to the crystallizer-separator unit in which the product is crystallized and separated intermittently or continuously; (3) the filtrate from the crystallizer-separator unit containing residual substrate is transferred to the substrate reservoir unit, where an additional amount of substrate is dissolved to make up the amount of substrate converted to the product during the last cycle; (4) the second-time filtered substrate solution from the substrate reservoir unit is fed back into the bioreactor proper unit for further bioconversion, and this completes the recycle loop of the new bioreactor-separator combination system. By this new design, a significant improvement in terms of product purity and production cost was achieved as compared to the conventional batch or semicontinuous bioconversion process systems. Based on our experimental results, we were able to conclude that highly pure amino acid product (>99.95% pure product) could be obtained, and at the same time, by employing this new biotransformation system the estimated production cost can be reduced by 25%, as compared to the conventional batch process system. It is anticipated that the principles involved in the design and operation of this new bioreactor system, as illustrated in this paper with an amino acid bioconversion process, from l-aspartate to l-alanine, as a model system will find many practical applications in the area of process biotechnology for products of pharmaceutical and agricultural importance.

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