Title |
Systems metabolic engineering of Escherichia coli for L‐threonine production
|
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Published in |
Molecular Systems Biology, December 2007
|
DOI | 10.1038/msb4100196 |
Pubmed ID | |
Authors |
Kwang Ho Lee, Jin Hwan Park, Tae Yong Kim, Hyun Uk Kim, Sang Yup Lee |
Abstract |
Amino-acid producers have traditionally been developed by repeated random mutagenesis owing to the difficulty in rationally engineering the complex and highly regulated metabolic network. Here, we report the development of the genetically defined L-threonine overproducing Escherichia coli strain by systems metabolic engineering. Feedback inhibitions of aspartokinase I and III (encoded by thrA and lysC, respectively) and transcriptional attenuation regulations (located in thrL) were removed. Pathways for Thr degradation were removed by deleting tdh and mutating ilvA. The metA and lysA genes were deleted to make more precursors available for Thr biosynthesis. Further target genes to be engineered were identified by transcriptome profiling combined with in silico flux response analysis, and their expression levels were manipulated accordingly. The final engineered E. coli strain was able to produce Thr with a high yield of 0.393 g per gram of glucose, and 82.4 g/l Thr by fed-batch culture. The systems metabolic engineering strategy reported here may be broadly employed for developing genetically defined organisms for the efficient production of various bioproducts. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 12 | 3% |
Germany | 4 | <1% |
China | 4 | <1% |
France | 4 | <1% |
Chile | 3 | <1% |
United Kingdom | 3 | <1% |
Sweden | 2 | <1% |
Denmark | 2 | <1% |
Australia | 1 | <1% |
Other | 8 | 2% |
Unknown | 381 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 110 | 26% |
Researcher | 68 | 16% |
Student > Master | 66 | 16% |
Student > Bachelor | 37 | 9% |
Student > Doctoral Student | 20 | 5% |
Other | 66 | 16% |
Unknown | 57 | 13% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 173 | 41% |
Biochemistry, Genetics and Molecular Biology | 75 | 18% |
Engineering | 53 | 13% |
Chemical Engineering | 10 | 2% |
Chemistry | 8 | 2% |
Other | 34 | 8% |
Unknown | 71 | 17% |