期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 108, 期 4, 页码 934-946出版社
WILEY-BLACKWELL
DOI: 10.1002/bit.22995
关键词
L-valine; fed-batch culture; in silico flux response analysis; systems metabolic engineering
资金
- Ministry of Education, Science and Technology
- Korean Systems Biology Research Project [20100002164]
- World Class University Program [R32-2008-000-10142-0]
We have previously reported the development of a 100% genetically defined engineered Escherichia coli strain capable of producing L-valine from glucose with a high yield of 0.38 g L-valine per gram glucose (0.58 mol L-valine per mol glucose) by batch culture. Here we report a systems biological strategy of employing flux response analysis in bioprocess development using L-valine production by fed-batch culture as an example. Through the systems-level analysis, the source of ATP was found to be important for efficient L-valine production. There existed a trade-off between L-valine production and biomass formation, which was optimized for the most efficient L-valine production. Furthermore, acetic acid feeding strategy was optimized based on flux response analysis. The final fed-batch cultivation strategy allowed production of 32.3 g/L L-valine, the highest concentration reported for E. coli. This approach of employing systems-level analysis of metabolic fluxes in developing fed-batch cultivation strategy would also be applicable in developing strategies for the efficient production of other bioproducts. Biotechnol. Bioeng. 2011;108: 934-946. (C) 2010 Wiley Periodicals, Inc.
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