Document Detail

Metabolic network analysis during fed-batch cultivation of Corynebacterium glutamicum for pantothenic acid production: first quantitative data and analysis of by-product formation.
MedLine Citation:
PMID:  12948644     Owner:  NLM     Status:  MEDLINE    
A first generation genetically modified strain of Corynebacterium glutamicum has been assessed for its potential to synthesise and accumulate the vitamin pantothenic acid in the medium using fed-batch cultivation technology, with biomass concentration controlled by isoleucine limitation. Kinetic analysis of specific rates throughout the process has been used to model carbon flux through both central metabolism and the specific pathways involved in product formation. Flux towards pantothenic acid is potentially high but much of this flux is dissipated as by-products within associated pathways, notably linked to amino acid synthesis. The major limitation of vitamin production in this strain is linked to the tenfold higher flux of keto-isovalerate towards valine rather than pantothenic acid. Attempts to modify this ratio by imposing nitrogen limitation provoked carbon overflow as unidentified non-nitrogenous compounds. The observed accumulation of glycine suggests that the flux towards pantothenate production may by limited by the rate of the pathway intermediate (5,10-methylene-tetrahydrofolate) regeneration.
Christophe Chassagnole; Audrey Diano; Fabien Létisse; Nic D Lindley
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Validation Studies    
Journal Detail:
Title:  Journal of biotechnology     Volume:  104     ISSN:  0168-1656     ISO Abbreviation:  J. Biotechnol.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-01     Completed Date:  2004-05-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8411927     Medline TA:  J Biotechnol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  261-72     Citation Subset:  IM    
Laboratoire Biotechnologie-Bioprocédés, UMR INSA/CNRS No. 5504, Centre de Bioingénierie Gilbert Durand, Institut National de Sciences Appliquées, 135 Avenue de Rangueil, F-31077 Toulouse cedex 4, France.
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MeSH Terms
Bioreactors / microbiology*
Cell Culture Techniques / methods*
Combinatorial Chemistry Techniques
Corynebacterium / genetics,  growth & development*,  metabolism*
Gene Expression Regulation, Bacterial / physiology*
Genetic Enhancement / methods*
Metabolism / physiology
Pantothenic Acid / biosynthesis*,  genetics
Pilot Projects
Reg. No./Substance:
79-83-4/Pantothenic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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