13c metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation13 c代谢通量分析确定一种不同寻常的方式在分枝杆菌丙酮酸异化需要异柠檬酸裂解酶和二氧化碳固定.pdfVIP

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13c metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation13 c代谢通量分析确定一种不同寻常的方式在分枝杆菌丙酮酸异化需要异柠檬酸裂解酶和二氧化碳固定.pdf

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13c metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation13 c代谢通量分析确定一种不同寻常的方式在分枝杆菌丙酮酸异化需要异柠檬酸裂解酶和二氧化碳固定

13C Metabolic Flux Analysis Identifies an Unusual Route for Pyruvate Dissimilation in Mycobacteria which Requires Isocitrate Lyase and Carbon Dioxide Fixation 1 1 2 2 2 Dany J. V. Beste , Bhushan Bonde , Nathaniel Hawkins , Jane L. Ward , Michael H. Beale , Stephan 3 ¨ 3 4 4 1 Noack , Katharina Noh , Nicholas J. Kruger , R. George Ratcliffe , Johnjoe McFadden * 1 School of Biomedical and Molecular Sciences, University of Surrey, Guildford, United Kingdom, 2 Rothamsted Research, National Centre for Plant and Microbial ¨ ¨ Metabolomics, Harpenden, Herts, United Kingdom, 3 Forschungszentrum Julich GmbH, Institute of Bio- and Geosciences 1: Biotechnology 2, Julich, Germany, 4 Department of Plant Sciences, University of Oxford, Oxford, United Kingdom Abstract Mycobacterium tuberculosis requires the enzyme isocitrate lyase (ICL) for growth and virulence in vivo. The demonstration that M. tuberculosis also requires ICL for survival during nutrient starvation and has a role during steady state growth in a glycerol limited chemostat indicates a function for this enzyme which extends beyond fat metabolism. As isocitrate lyase is a potential drug target elucidating the role of this enzyme is of importance; however, the role of isocitrate lyase has never been investigated at the level of in vivo fluxes. Here we show that deletion of one of the two icl genes impairs the replication of Mycobacterium bovis BCG at slow growth rate in a carbon limited chemostat. In