From zero to hero—Design-based systems metabolic engineering of Corynebacterium glutamicum for l-lysine production

Here, we describe the development of a genetically defined strain of l-lysine hyperproducing Corynebacterium glutamicum by systems metabolic engineering of the wild type. Implementation of only 12 defined genome-based changes in genes encoding central metabolic enzymes redirected major carbon fluxes...

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Bibliographic Details
Published in:	Metabolic engineering Vol. 13; no. 2; pp. 159 - 168
Main Authors:	Becker, Judith, Zelder, Oskar, Häfner, Stefan, Schröder, Hartwig, Wittmann, Christoph
Format:	Journal Article
Language:	English
Published:	Belgium Elsevier Inc 01.03.2011
Subjects:	carbon Corynebacterium glutamicum Corynebacterium glutamicum - genetics Corynebacterium glutamicum - metabolism enzymes Fermentation - genetics genes Genetic Engineering glucose Glucose - metabolism In silico design industrial applications Industrial Microbiology - methods lysine Lysine - biosynthesis Lysine - genetics metabolic engineering Metabolic flux analysis Metabolic Networks and Pathways - genetics Models, Biological Rational strain optimization Systems biology In silico design Rational strain optimization Systems biology Metabolic flux analysis
ISSN:	1096-7176, 1096-7184, 1096-7184
Online Access:	Get full text
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Summary:	Here, we describe the development of a genetically defined strain of l-lysine hyperproducing Corynebacterium glutamicum by systems metabolic engineering of the wild type. Implementation of only 12 defined genome-based changes in genes encoding central metabolic enzymes redirected major carbon fluxes as desired towards the optimal pathway usage predicted by in silico modeling. The final engineered C. glutamicum strain was able to produce lysine with a high yield of 0.55 g per gram of glucose, a titer of 120 g L −1 lysine and a productivity of 4.0 g L −1 h −1 in fed-batch culture. The specific glucose uptake rate of the wild type could be completely maintained during the engineering process, providing a highly viable producer. For these key criteria, the genetically defined strain created in this study lies at the maximum limit of classically derived producers developed over the last fifty years. This is the first report of a rationally derived lysine production strain that may be competitive with industrial applications. The design-based strategy for metabolic engineering reported here could serve as general concept for the rational development of microorganisms as efficient cellular factories for bio-production.
Bibliography:	http://dx.doi.org/10.1016/j.ymben.2011.01.003 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1096-7176 1096-7184 1096-7184
DOI:	10.1016/j.ymben.2011.01.003