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

Tsuneo Yamane, Pramote Sirirote, Shoichi Shimizu
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引用次数: 4

Abstract

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.

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增加细胞质量浓度对代谢物产生的经济意义-理论研究-
从理论上讨论了增加细胞质量到高浓度生产代谢物的经济意义。首先,代谢物生产的直接成本已被制定为原材料成本、运行成本和直接人工成本的总和。根据定义,原料成本与消耗的养分的代谢物产量有关,运行成本与形成的代谢物的生产率(或时空产量)有关。高细胞质量浓度补料分批培养的两个特点,即培养液的总体积增加和总培养液中湿细胞的一定体积占用,已被数学考虑。1.(1)当代谢物在细胞内积累时,在细胞代谢产物含量最高的最短工作时间内,从消耗的一定量的营养物质中获得最多的细胞,从而使直接生产成本最小化。在两阶段培养法中(细胞生长早期和代谢物积累阶段),细胞质量浓度的增加对原料成本的降低作用不大,但确实降低了运行成本。(2)当代谢物在培养上清中细胞外积累时,原料成本随着一定数量的原料形成的细胞质量产量的增加而增加。只有提高代谢物产率,才能降低原料成本。运行成本往往会随着细胞质量浓度的增加而降低。在生产胞外代谢物的两阶段培养法中,除非第二阶段的代谢物产量占主导地位,否则原料成本随着细胞质量浓度的增加而增加,而通常存在一个特定的细胞质量浓度,在该浓度下运行成本最小。
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