HIGH CELL-DENSITY CULTIVATION OF ESCHERICHIA-COLI AT CONTROLLED SPECIFIC GROWTH-RATE

HIGH CELL-DENSITY CULTIVATION OF ESCHERICHIA-COLI AT CONTROLLED SPECIFIC GROWTH-RATE
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DOI:
10.1016/0168-1656(91)90032-q
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发表时间:
1991-08-01
影响因子:
4.1
通讯作者:
DECKWER, WD
DECKWER, WD
中科院分区:
工程技术3区
文献类型:
--
作者:
RIESENBERG, D;SCHULZ, V;DECKWER, WD

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提出了一种在特殊设计的葡萄糖/无机盐培养基中培养大肠杆菌的高密度培养方法。HCDC基本上是以批处理开始的,然后是两阶段的饲料批培养。在分批培养阶段,在mu-(max) = 0.45 h-1的条件下无限制生长后,在生物量浓度从12 g - l-1增加到95 g - l-1的3倍周期(投料分批培养阶段1)内,以较低的比生长率(mu = 0.11 h-1 < mu-(max))控制生长。生长(mu)通过pO2控制回路(通过改变葡萄糖投料)和mu控制回路(通过改变搅拌速度N)实现控制,实际mu由废气组成计算。如果搅拌速率不能再增加,mu控制器被关闭(阶段1结束)。在接下来的第二阶段,亩数下降,但pO2(葡萄糖)控制器仍然起作用,保证了足够的氧气供应,直到培养结束,生物量浓度为110 g l-1(干质量)。提出的HCDC抑制了抑制副产物的产生,高产系数表明该工艺的经济性。
A high cell density cultivation (HCDC) for growth of Escherichia coli in an especially designed glucose/mineral salt medium is proposed. The HCDC essentially starts as a batch process which is followed by a two-phase fed-batch cultivation. After unlimited growth at mu-(max) = 0.45 h-1 in the batch part, growth was controlled at a reduced specific growth rate (mu = 0.11 h-1 < mu-(max)) over a period of 3 doubling times in which the biomass concentration increased from 12 to 95 g l-1 (phase 1 of fed-batch cultivation). Control of growth (mu) was realized by a pO2 control loop (by variation of glucose feeding) and a mu control loop (by variation of agitation speed N) while the actual mu was calculated from the off-gas composition. If the agitation rate cannot be increased anymore the mu controller is switched off (end of phase 1). In the following phase 2, mu declines, however, the still acting pO2 (glucose) controller guarantees sufficient O2 supply till the end of the cultivation with a biomass concentration of 110 g l-1 (dry mass). The proposed HCDC suppresses generation of inhibitory by-products and the high yield coefficients indicate the economy of the process.