Abstract
Metabolic flux analysis (MFA) is a computationally-dependent mathematical framework which can be used for determining the more representative variables of a biological system; MFA can be greatly improved by means of a sensitivity analysis (SA). In this work, we used a SA and a MFA to study the Streptomyces clavuligerus metabolism for clavulanic acid (CA) production. It was observed that the measured metabolic fluxes that significantly affected the cellular system were phenylalanine, isoleucine, tyrosine and lysine. According to the flux distribution at two dilution rates (D), the biosynthesis of CA was favored at low D, leading to higher values in the precursor fluxes of the tricarboxylic acid and urea cycles. Moreover, it was found that the flux of ornithine, rather than the flux of arginine, affects the biosynthesis of CA, which evidences the importance of controlling the flux of carbon through the urea cycle.
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References
Lee, S.H., Kim, J., Park, J., Kim, T.: Metabolic Engineering of Microorganisms: General Strategies and Drug Production. Drug Discovery Today 14(1-2), 78–88 (2009)
Kohlstedt, M., Becker, J., Wittmann, C.: Metabolic Fluxes and Beyond. Applied Microbiology and Biotechnology 88, 1065–1075 (2010)
Kirk, S., Avignone-Rossa, C., Bushell, M.: Growth Limiting Substrate Affects Antibiotic production and Associated Metabolic Fluxes in Streptomyces clavuligerus. Biotechnology Letters 22, 1803–1809 (2000)
Bushell, M., Kirk, S.Z., Avignone-Rosa, C.: Manipulation of the Physiology of Clavulanic Acid Biosynthesis with the aid of Metabolic Flux Analysis. Enzyme and Microbial Technology 39(1), 149–157 (2006)
Daae, E., Ison, A.: Classification and Sensitivity Analysis of a Proposed Primary Metabolic Network for Streptomyces Lividans. Metabolic Eng. 1(2), 53–165 (1999)
Sánchez, C., Gómez, N., Quintero, J.: Producción de Ácido clavulánico por fermentación de Streptomyces Clavuligerus. Dyna 175, 158–165 (2012)
Klamt, S.: CellNet Analyzer, Structural Analysis of Cellular Networks, Version 9.6, Max-Planck-Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany (2011)
Naeimpoor, F., Mavituna, F.: Metabolic Flux Analysis in Streptomyces coelicolor under Various Nutrient Limitations. Metabolic Engineering 2(2), 140–148 (2000)
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Sánchez, C., Gómez, N., Quintero, J.C., Ochoa, S., Rios, R. (2014). A Combined Sensitivity and Metabolic Flux Analysis Unravel the Importance of Amino Acid Feeding Strategies in Clavulanic Acid Biosynthesis. In: Castillo, L., Cristancho, M., Isaza, G., Pinzón, A., Rodríguez, J. (eds) Advances in Computational Biology. Advances in Intelligent Systems and Computing, vol 232. Springer, Cham. https://doi.org/10.1007/978-3-319-01568-2_25
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DOI: https://doi.org/10.1007/978-3-319-01568-2_25
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-01567-5
Online ISBN: 978-3-319-01568-2
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