| Structure Identification: |
| J Ind Microbiol Biotechnol. 2006 Jul;33(7):610-5. | | A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production[Pubmed: 16506038 ] |
METHODS AND RESULTS:
Based on the progress in genomics, we have developed a novel approach that employs genomic information to generate an efficient amino acid producer. A comparative genomic analysis of an industrial L-lysine producer with its natural ancestor identified a variety of mutations in genes associated with L-lysine biosynthesis. Among these mutations, we identified two mutations in the relevant terminal pathways as key mutations for L-lysine production, and three mutations in central metabolism that resulted in increased titers. These five mutations when assembled in the wild-type genome led to a significant increase in both the rate of production and final L-lysine titer. Further investigations incorporated with transcriptome analysis suggested that other as yet unidentified mutations are necessary to support the L-lysine titers observed by the original production strain.
CONCLUSIONS:
Here we describe the essence of our approach for strain reconstruction, and also discuss mechanisms of L-lysine hyperproduction unraveled by combining genomics with classical strain improvement. | | Bioconjug Chem. 1999 Jan-Feb;10(1):137-40. | | L-Glutamic acid and L-lysine as useful building blocks for the preparation of bifunctional DTPA-like ligands.[Pubmed: 9893975 ] |
METHODS AND RESULTS:
Bisalkylation of suitably protected L-glutamic acid and L-lysine derivatives with tert-butyl N-(2-bromoethyl)iminodiacetate 2, followed by deprotection of the omega functional group affords N, N-bis[2-[bis[2-(1, 1-dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-glutamic acid 1-(1, 1-dimethylethyl) ester 4 and N2,N2-bis[2-[bis[2-(1, 1-dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-lysine 1,1-dimethylethyl ester 7. Such compounds feature a carboxylic or an amino group, respectively, which are available for conjugation with a suitable partner via formation of an amide bond.
CONCLUSIONS:
The conjugates, which can be prepared in this way, contain a chelating subunit in which all five acetic residues of DTPA are available for the complexation of metal ions. Direct bisalkylation of glycine with 2 promptly gives N, N-bis[2-[bis[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]ethyl]glycine 11. The latter allows to achieve conjugates in which the central acetic group of DTPA is selectively converted into an acetamide. |
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