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Lysine overproducing Corynebacterium glutamicum is characterized by a robust linear combination of two optimal phenotypic states

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Systems and Synthetic Biology

Abstract

A homoserine auxotroph strain of Corynebacterium glutamicum accumulates storage compound trehalose with lysine when limited by growth. Industrially lysine is produced from C. glutamicum through aspartate biosynthetic pathway, where enzymatic activity of aspartate kinase is allosterically controlled by the concerted feedback inhibition of threonine plus lysine. Ample threonine in the medium supports growth and inhibits lysine production (phenotype-I) and its complete absence leads to inhibition of growth in addition to accumulating lysine and trehalose (phenotype-II). In this work, we demonstrate that as threonine concentration becomes limiting, metabolic state of the cell shifts from maximizing growth (phenotype-I) to maximizing trehalose phenotype (phenotype-II) in a highly sensitive manner (with a Hill coefficient of 4). Trehalose formation was linked to lysine production through stoichiometry of the network. The study demonstrated that the net flux of the population was a linear combination of the two optimal phenotypic states, requiring only two experimental measurements to evaluate the flux distribution. The property of linear combination of two extreme phenotypes was robust for various medium conditions including varying batch time, initial glucose concentrations and medium osmolality.

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Acknowledgments

KVV acknowledges financial support for research from Department of Science and Technology, India. Authors are thankful to Dr. M. G. Poolman and Prof. D. A. Fell (Oxford Brooks University) for providing the “ScrumPy” software. Authors are also thankful to Prof. Sharad Bhartiya and Dr P. K. Vinod for their useful suggestions.

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Authors and Affiliations

  1. Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India

    Meghna Rajvanshi

  2. Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India

    Kalyan Gayen & K. V. Venkatesh

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  1. Meghna Rajvanshi
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  2. Kalyan Gayen
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  3. K. V. Venkatesh
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Correspondence to K. V. Venkatesh.

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Rajvanshi, M., Gayen, K. & Venkatesh, K.V. Lysine overproducing Corynebacterium glutamicum is characterized by a robust linear combination of two optimal phenotypic states. Syst Synth Biol 7, 51–62 (2013). https://doi.org/10.1007/s11693-013-9107-5

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  • DOI: https://doi.org/10.1007/s11693-013-9107-5

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