Process control for enhanced L-phenylalanine production using different recombinant Escherichia coli strains
Process control for enhanced L-phenylalanine production using different recombinant Escherichia coli strains
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DOI：
10.1002/bit.10428
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发表时间：
2002-12-30
影响因子：
3.8
通讯作者：
Takors, R
中科院分区：
文献类型：
--
作者：
Gerigk, M;Bujnicki, R;Takors, R
提出了一种利用重组大肠杆菌分批补料生产L-苯丙氨酸(L-苯丙氨酸)的新方法，并对发酵关键参数葡萄糖和酪氨酸进行了在线控制。以两株不同的生产菌株为模型系统，分别具有抗酪氨酸反馈的aroF(FBR)(编码抗酪氨酸反馈的DAHP合酶(3-脱氧-D-阿拉伯庚酸-7-磷酸))和野生型aroF(Wt)，以阐明为每个基因寻找一个单独的工艺最佳的必要性。在酪氨酸控制的辅助下，野生型aroF(Wt)可用于生产L-Phe，最终L-Phe效价(34g/L)高于aroF(Fbr)菌株(28g/L)，并提供更高的DAHP-合成酶活性。通过在线血糖控制，可以确定最适葡萄糖浓度为5g/L，以保证L-苯丙氨酸生产所需的碳源充足，同时避免了导致乙酸酯副产物生成的代谢溢出。该工艺方法不仅适用于实验室规模的其他生产菌株，也适用于中试规模的生物反应器。(C)2002年威利期刊公司。
A novel fed-batch approach for the production of L-phenylalanine (L-Phe) with recombinant E. coli is presented concerning the on-line control of the key fermentation parameters glucose and tyrosine. Two different production strains possessing either the tyrosine feedback resistant aroF(fbr) (encoding tyrosine feedback resistant DAHP-synthase (3-desoxy-D-arabinoheptusonate-7-phosphate)) or the wild-type aroF(wt) were used as model systems to elucidate the necessity of finding an individual process optimum for each genotype. With the aid of tyrosine control, wild-type aroF(wt) could be used for L-Phe production achieving higher final L-Phe titers (34 g/L) than the aroF(fbr) strain (28 g/L) and providing higher DAHP-synthase activities. With on-line glucose control, an optimum glucose concentration of 5 g/L could be identified that allowed a sufficient carbon supply for L-Phe production while at the same time an overflow metabolism leading to acetate by-product formation was avoided. The process approach is suitable for other production strains not only in lab-scale but also in pilot-scale bioreactors. (C) 2002 Wiley Periodicals, Inc.