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This title appears in the Scientific Report : 2010 

Importance of NADPH supply for improved L-valine formation in Corynebacterium glutamicum

Importance of NADPH supply for improved L-valine formation in Corynebacterium glutamicum

Cofactor recycling is known to be crucial for amino acid synthesis. Hence, cofactor supply was now analyzed for L-valine to identify new targets for an improvement of production. The central carbon metabolism was analyzed by stoichiometric modeling to estimate the influence of cofactors and to quant...

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Personal Name(s): Bartek, T.
Blombach, B. / Zoennchen, E. / Makus, P. / Lang, S. / Eikmanns, B. / Oldiges, M.
Contributing Institute: Biotechnologie 2; IBT-2
Published in: Biotechnology progress (2010) S. 361-371
Imprint: Malden, MA Wiley 2010
Physical Description: 361-371
PubMed ID: 20014412
DOI: 10.1002/btpr.345
Document Type: Journal Article
Research Program: Biotechnologie
Series Title: Biotechnology Progress 26
Subject (ZB):
Cell Culture Techniques
Corynebacterium glutamicum: enzymology
Corynebacterium glutamicum: genetics
Corynebacterium glutamicum: metabolism
Culture Media
Fermentation
Glucose-6-Phosphate Isomerase: genetics
Metabolic Networks and Pathways
Metabolome
Models, Biological
NADP: metabolism
Valine: metabolism
NADP
Valine
Glucose-6-Phosphate Isomerase
J
valine
metabolome analysis
NADPH
fermentation
stoichiometric modeling
Publikationsportal JuSER
Please use the identifier: http://dx.doi.org/10.1002/btpr.345 in citations.

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Cofactor recycling is known to be crucial for amino acid synthesis. Hence, cofactor supply was now analyzed for L-valine to identify new targets for an improvement of production. The central carbon metabolism was analyzed by stoichiometric modeling to estimate the influence of cofactors and to quantify the theoretical yield of L-valine on glucose. Three different optimal routes for L-valine biosynthesis were identified by elementary mode (EM) analysis. The modes differed mainly in the manner of NADPH regeneration, substantiating that the cofactor supply may be crucial for efficient L-valine production. Although the isocitrate dehydrogenase as an NADPH source within the tricarboxylic acid cycle only enables an L-valine yield of Y(Val/Glc) = 0.5 mol L-valine/mol glucose (mol Val/mol Glc), the pentose phosphate pathway seems to be the most promising NADPH source. Based on the theoretical calculation of EMs, the gene encoding phosphoglucoisomerase (PGI) was deleted to achieve this EM with a theoretical yield Y(Val/Glc) = 0.86 mol Val/mol Glc during the production phase. The intracellular NADPH concentration was significantly increased in the PGI-deficient mutant. L-Valine yield increased from 0.49 +/- 0.13 to 0.67 +/- 0.03 mol Val/mol Glc, and, concomitantly, the formation of by-products such as pyruvate was reduced.

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