INCOMPLETE MIXING IN LARGE BIOREACTORS - A STUDY OF ITS ROLE IN THE FERMENTATIVE PRODUCTION OF STREPTOKINASE

The production of streptokinase in a batch fermentation has been analy sed for the role of incomplete macromixing of the broth. The analysis is based on a kinetic model exhibiting inhibition by the substrate and a primary metabolite (lactic acid), and a mixing model comprising two continuous flow reactors (CFRs) with closed-loop recycle. The inoculu m is introduced into one region (one CFR) and the mixing process deter mines its distribution, growth and reactivity. By varying the dilution rates of the CFRs, any degree of macromixing can be simulated. For di lution rates larger than 1.0 h(-1) almost complete macromixing is achi eved, for which an analogy has been drawn with micromixing. Increasing the volume of the inoculated region relative to the noninoculated reg ion improves the maximum attainable activity of streptokinase and shor tens the time for this. In such a situation an imperfectly mixed biore actor is superior to a perfectly mixed one, implying that good product ivity requires a large inoculated region and incomplete macromixing. T hese inferences are supported by earlier studies of fluid mixing and r elaxation times in bioreactors.