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

Mahr R, Gaetgens C, Gaetgens J, Polen T, Kalinowski J, Frunzke J (2015)
Metabolic Engineering 32: 184-194.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Mahr, Regina; Gaetgens, Cornelia; Gaetgens, Jochem; Polen, Tino; Kalinowski, JörnUniBi; Frunzke, Julia
Abstract / Bemerkung
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 Delta aceE 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 (similar to 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. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
Stichworte
Biosensor
Erscheinungsjahr
2015
Zeitschriftentitel
Metabolic Engineering
Band
32
Seite(n)
184-194
ISSN
1096-7176
eISSN
1096-7184
Page URI
https://pub.uni-bielefeld.de/record/2901032

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Mahr R, Gaetgens C, Gaetgens J, Polen T, Kalinowski J, Frunzke J. Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metabolic Engineering. 2015;32:184-194.
Mahr, R., Gaetgens, C., Gaetgens, J., Polen, T., Kalinowski, J., & Frunzke, J. (2015). Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metabolic Engineering, 32, 184-194. doi:10.1016/j.ymben.2015.09.017
Mahr, Regina, Gaetgens, Cornelia, Gaetgens, Jochem, Polen, Tino, Kalinowski, Jörn, and Frunzke, Julia. 2015. “Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum”. Metabolic Engineering 32: 184-194.
Mahr, R., Gaetgens, C., Gaetgens, J., Polen, T., Kalinowski, J., and Frunzke, J. (2015). Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metabolic Engineering 32, 184-194.
Mahr, R., et al., 2015. Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metabolic Engineering, 32, p 184-194.
R. Mahr, et al., “Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum”, Metabolic Engineering, vol. 32, 2015, pp. 184-194.
Mahr, R., Gaetgens, C., Gaetgens, J., Polen, T., Kalinowski, J., Frunzke, J.: Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metabolic Engineering. 32, 184-194 (2015).
Mahr, Regina, Gaetgens, Cornelia, Gaetgens, Jochem, Polen, Tino, Kalinowski, Jörn, and Frunzke, Julia. “Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum”. Metabolic Engineering 32 (2015): 184-194.

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