Metabolic Contest, a New Way to Control Carbon Source Preference

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Allmann, Stefan | Wargnies, Marion | Cahoreau, Edern | Biran, Marc | Plazolles, Nicolas | Morand, Pauline | Pineda, Erika | Kulyk, Hanna | Asencio, Corinne | Villafraz, Oriana | Rivière, Loïc | Tetaud, Emmanuel | Rotureau, Brice | Mourier, Arnaud | Portais, Jean-Charles | Bringaud, Frédéric

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Prépublication. SUMMARY Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, allowing to redirect cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism, named ``metabolic contest'', for regulating the use of carbon sources without nutrient sensing and signaling. In contrast to most microorganisms, trypanosomes show a glycerol-to-glucose preference that depends on the combination of three conditions: ( i ) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-like organelles named glycosomes; ( ii ) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways being both ATP-dependent (glycerol kinase and hexokinase, respectively) and ( iii ) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being ~80-fold higher than the hexokinase activity.

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