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Metabolites 2015, 5(2), 211-231; doi:10.3390/metabo5020211

Fermentative Production of the Diamine Putrescine: System Metabolic Engineering of Corynebacterium Glutamicum

Chair of Genetics of Prokaryotes, Faculty of Biology & CeBiTec, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany
Current Address: Evonik Industries AG, Kantstra
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Author to whom correspondence should be addressed.
Academic Editor: Dirk Steinhauser
Received: 26 February 2015 / Revised: 8 April 2015 / Accepted: 13 April 2015 / Published: 24 April 2015
(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology)
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Abstract

Corynebacterium glutamicum shows great potential for the production of the glutamate-derived diamine putrescine, a monomeric compound of polyamides. A genome-scale stoichiometric model of a C. glutamicum strain with reduced ornithine transcarbamoylase activity, derepressed arginine biosynthesis, and an anabolic plasmid-addiction system for heterologous expression of E. coli ornithine decarboxylase gene speC was investigated by flux balance analysis with respect to its putrescine production potential. Based on these simulations, enhancing glycolysis and anaplerosis by plasmid-borne overexpression of the genes for glyceraldehyde 3-phosphate dehydrogenase and pyruvate carboxylase as well as reducing 2-oxoglutarate dehydrogenase activity were chosen as targets for metabolic engineering. Changing the translational start codon of the chromosomal gene for 2-oxoglutarate dehydrogenase subunit E1o to the less preferred TTG and changing threonine 15 of OdhI to alanine reduced 2-oxoglutarate dehydrogenase activity about five fold and improved putrescine titers by 28%. Additional engineering steps improved further putrescine production with the largest contributions from preventing the formation of the by-product N-acetylputrescine by deletion of spermi(di)ne N-acetyltransferase gene snaA and from overexpression of the gene for a feedback-resistant N-acetylglutamate kinase variant. The resulting C. glutamicum strain NA6 obtained by systems metabolic engineering accumulated two fold more putrescine than the base strain, i.e., 58.1 ± 0.2 mM, and showed a specific productivity of 0.045 g·g−1·h−1 and a yield on glucose of 0.26 g·g−1. View Full-Text
Keywords: diamine production; putrescine; Corynebacterium glutamicum; 2-oxoglutatarate dehydrogenase; pyruvate carboxylase; glyceraldehyde 3-phosphate dehydrogenase; OdhI; spermidine N-acetyltransferase; CgmR; N-acetylglutamate kinase; gamma-glutamate kinase; genome-scale metabolic model; flux balance analysis diamine production; putrescine; Corynebacterium glutamicum; 2-oxoglutatarate dehydrogenase; pyruvate carboxylase; glyceraldehyde 3-phosphate dehydrogenase; OdhI; spermidine N-acetyltransferase; CgmR; N-acetylglutamate kinase; gamma-glutamate kinase; genome-scale metabolic model; flux balance analysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Nguyen, A.Q.D.; Schneider, J.; Reddy, G.K.; Wendisch, V.F. Fermentative Production of the Diamine Putrescine: System Metabolic Engineering of Corynebacterium Glutamicum. Metabolites 2015, 5, 211-231.

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