Fed-Batch Culture of Escherichia coli for L-Valine Production Based on In Silico Flux Response Analysis

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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.
Publisher
WILEY-BLACKWELL
Issue Date
2011-04
Language
English
Article Type
Article
Keywords

CORYNEBACTERIUM-GLUTAMICUM; K-12; GENE; GROWTH; MUTANT

Citation

BIOTECHNOLOGY AND BIOENGINEERING, v.108, no.4, pp.934 - 946

ISSN
0006-3592
DOI
10.1002/bit.22995
URI
http://hdl.handle.net/10203/95156
Appears in Collection
CBE-Journal Papers(저널논문)
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