Combining rational metabolic engineering and flux optimization strategies for efficient production of fumaric acid

Verfasser / Beitragende:
[Chan Song, Sang Lee]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/20(2015-10-01), 8455-8464
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-015-6816-6  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6816-6 
245 0 0 |a Combining rational metabolic engineering and flux optimization strategies for efficient production of fumaric acid  |h [Elektronische Daten]  |c [Chan Song, Sang Lee] 
520 3 |a Fumaric acid is an important C4-dicarboxylic acid widely used in chemical, food, and pharmaceutical industries. Rational metabolic engineering together with flux optimization were performed for the development of an Escherichia coli strain capable of efficiently producing fumaric acid. The initial engineered strain, CWF4N overexpressing phosphoenolpyruvate carboxylase (PPC), produced 5.30g/L of fumaric acid. Optimization of PPC flux by examining 24 types of synthetic PPC expression vectors further increased the titer up to 5.72g/L with a yield of 0.432g/g·glucose. Overexpression of the succinate dehydrogenase complex (sdhCDAB) led to an increase in carbon yield up to 0.493g/g·glucose. Based on this mutant strain, citrate synthase (CS) was combinatorially overexpressed and balanced with PPC using 48 types of synthetic expression vectors. As a result, 6.24g/L of fumaric acid was produced with a yield of 0.500g/g·glucose. Fed-batch culture of this final strain allowed production of 25.5g/L of fumaric acid with a yield of 0.366g/g·glucose. Deletion of the aspA gene encoding aspartase and supplementation of aspartic acid further increased the fumaric acid titer to 35.1g/L with a yield of 0.490g/g·glucose. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Fumaric acid  |2 nationallicence 
690 7 |a Escherichia coli  |2 nationallicence 
690 7 |a Flux optimization  |2 nationallicence 
690 7 |a Metabolic engineering  |2 nationallicence 
700 1 |a Song  |D Chan  |u Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 305-701, Daejeon, Republic of Korea  |4 aut 
700 1 |a Lee  |D Sang  |u Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 305-701, Daejeon, Republic of Korea  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/20(2015-10-01), 8455-8464  |x 0175-7598  |q 99:20<8455  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6816-6  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6816-6  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Song  |D Chan  |u Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 305-701, Daejeon, Republic of Korea  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lee  |D Sang  |u Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 305-701, Daejeon, Republic of Korea  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/20(2015-10-01), 8455-8464  |x 0175-7598  |q 99:20<8455  |1 2015  |2 99  |o 253