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Metab Eng. 2015 Nov;32:184-194. doi: 10.1016/j.ymben.2015.09.017. Epub 2015 Oct 8.

Biosensor-driven adaptive laboratory evolution of l-valine production in Corynebacterium glutamicum.

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IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany.
IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany. Electronic address:


Adaptive laboratory evolution has proven a valuable strategy for metabolic engineering. Here, we established an experimental evolution approach for improving microbial metabolite production by imposing an artificial selective pressure on the fluorescent output of a biosensor using fluorescence-activated cell sorting. Cells showing the highest fluorescent output were iteratively isolated and (re-)cultivated. The L-valine producer Corynebacterium glutamicum ΔaceE was equipped with an L-valine-responsive sensor based on the transcriptional regulator Lrp of C. glutamicum. Evolved strains featured a significantly higher growth rate, increased L-valine titers (~25%) and a 3-4-fold reduction of by-product formation. Genome sequencing resulted in the identification of a loss-of-function mutation (UreD-E188*) in the gene ureD (urease accessory protein), which was shown to increase L-valine production by up to 100%. Furthermore, decreased L-alanine formation was attributed to a mutation in the global regulator GlxR. These results emphasize biosensor-driven evolution as a straightforward approach to improve growth and productivity of microbial production strains.


Adaptive laboratory evolution; Biosensor; Corynebacterium glutamicum; L-valine; Metabolic engineering; Transcription factor

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