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Mutat Res. 2008 Jan 8;649(1-2):239-44. Epub 2007 Oct 18.

Characterization of mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in an industrial Corynebacterium glutamicum strain.

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Bio-Frontier Laboratories, Kyowa Hakko Kogyo Co Ltd, Machida, Tokyo, Japan.


Mutations induced by classical whole-cell mutagenesis using N-methyl-N'-nitro-N-nitrosoguanidine (NTG) were determined for all genes of pathways from glucose to L-lysine in an industrial L-lysine producer of Corynebacterium glutamicum. A total of 50 mutations with a genome-wide distribution were identified and characterized for mutational types and mutagenic specificities. Those mutations were all point mutations with single-base substitutions and no deletions, frame shifts, and insertions were found. Among six possible types of base substitutions, the mutations consisted of only two types: 47 G.C-->A.T transitions and three A.T-->G.C transitions with no transversion. The findings indicate a limited repertoire of amino acid substitutions by classical NTG mutagenesis and thus raise a new possibility of further improving industrial strains by optimizing key mutations through PCR-mediated site-directed mutagenesis.

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