Metabolic approaches for the production of amino acids with Corynebacterium glutamicum
1995
Sahm, H. | Eikmanns, B.J. | Eggeling, L. (Forschungszentrum Juelich GmbH, Juelich (Germany). Inst. fuer Biotechnologie)
The gram-positive bacterium Corynebacterium glutamicum is used for the industrial production of amino acids, e.g. of L-glutamate and L-lysine. By cloning and expressing the various genes of the L-lysine pathway in C. glutamicum we could demonstrate that an increase of the flux of L-aspartate semialdehyde to L-lysine could be obtained in strains with increased dihydrodipicolinate synthase activity. Recently we detected that in C glutamicum two pathways exist for the synthesis of D,L-diaminopimelate and L-lysine. Mutants defect in one pathway are still able to synthesize enough L-lysine for growth but the L-lysine secretion is reduced to 50-70 per cent. Using NMR-spectroscopy we could calculate how much of the L-lysine secreted into the medium is synthesized via the one and the other pathway. Amplification of the feedback inhibition insensitive homoserine dehydrogenase and homoserine kinase in a high L-lysine overproducing strain enabled channelling of the carbon flow from the intermediate aspartate semialdehyde towards homoserine, resulting in a high accumulation of L-threonine. For a further flux from L-threonine to Lisoleucine the allosteric control of threonine dehydratase was eliminated. By this way the L-threonine production was shifted to L-isoleucine secretion in the range of 20 g per liter.
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