Economic significance of increasing cell mass concentration for metabolite production -A theoretical study-

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The economic significance of increasing cell mass to high concentrations for metabolite production has been discussed theoretically. First, the direct cost of the metabolite production has been formulated as the sum of the raw material cost, the running cost, and the direct labor cost. By definition, the raw material cost is related to the metabolite yield from the nutrient consumed and the running cost is related to the productivity (or space-time yield) of the metabolite formed. Two characteristics of fed-batch culture at high cell mass concentration, i.e. the increase in the total volume of the culture broth and a definite volumetric occupation of wet cells in the total culture broth, have been taken into mathematical consideration. 1. (1) When the metabolite accumulates intracellularly, the direct production cost is minimized by obtaining the greatest amount of cells from a fixed amount of the nutrient consumed in the shortest operating time at which the cells have the highest content of the metabolite under consideration. In the two stage cultivation method (the early cell growth phase followed by the metabolite accumulation phase), an increase in cell mass concentration reduces the raw material cost only a little, but it does reduce the running cost. 2. (2) When the metabolite accumulates extracellularly in the culture supernatant, the raw material cost rises with increasing yield of the cell mass which is formed from a given amount of the raw material. The raw material cost cannot be lowered unless the metabolite yield is raised. The running cost tends to be reduced by increases in the cell mass concentration. In the two-stage cultivation method of extracellular metabolite production, the raw material cost increases with increasing cell mass concentration unless the metabolite yield at the second phase is predominant, while there is usually a particular cell mass concentration at which the running cost is minimized.