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One of the most commonly used approaches for improving the production of L-Lysine in Corynebacterium glutamicum was classical mutagenesis which involves the repeated mutation and selection of the desired mutant. Single and/ or combined cloning and expression of the genes or disruption of certain genes in Corynebacterium glutamicum enabled the analysis of carbon flux control in response to elevation or removal of the respective enzyme activity. Based on these analyses, new strategies for the manipulation of this industrially important amino acid producer become possible. A quantitative description of how a pathway flux is controlled by individual pathway reactions and how this control changes in response to environmental and genetic changes will provide a rational basis for genetic manipulation. The key aspect of this approach is to enable a production strain to make full use of its intrinsic ability through eliminating all undesirable mutations accumulated in its genome. This review focuses on the approaches in the last 30 years in the field of industrial production of L-Lysine by Corynebacterium glutamicum from conventional methods like classical mutagenesis, metabolic flux analysis to the recent advancements like DNA microarray, genome based strain breeding and genome sequencing and functional genomics. This review also explains about the accomplishments by different approaches to the strain improvement in Corynebacterium glutamicum and also gives an insight for rationalizing production mechanism.
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