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The threonine degradation pathway of the T rypanosoma brucei procyclic form: the main carbon source for lipid biosynthesis is under metabolic control
Author(s) -
Millerioux Yoann,
Ebikeme Charles,
Biran Marc,
Morand Pauline,
Bouyssou Guillaume,
Vincent Isabel M.,
Mazet Muriel,
Riviere Loïc,
Franconi JeanMichel,
Burchmore Richard J. S.,
Moreau Patrick,
Barrett Michael P.,
Bringaud Frédéric
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12351
Subject(s) - threonine , biochemistry , phosphoenolpyruvate carboxykinase , biology , amino acid synthesis , metabolic pathway , trypanosoma brucei , biosynthesis , amino acid , mutant , enzyme , metabolism , lipid metabolism , glycolysis , serine , gene , lysine
Summary The T rypanosoma brucei procyclic form resides within the digestive tract of its insect vector, where it exploits amino acids as carbon sources. Threonine is the amino acid most rapidly consumed by this parasite, however its role is poorly understood. Here, we show that the procyclic trypanosomes grown in rich medium only use glucose and threonine for lipid biosynthesis, with threonine's contribution being ∼ 2.5 times higher than that of glucose. A combination of reverse genetics and NMR analysis of excreted end‐products from threonine and glucose metabolism, shows that acetate, which feeds lipid biosynthesis, is also produced primarily from threonine. Interestingly, the first enzymatic step of the threonine degradation pathway, threonine dehydrogenase ( TDH , EC 1.1.1.103), is under metabolic control and plays a key role in the rate of catabolism. Indeed, a trypanosome mutant deleted for the phosphoenolpyruvate decarboxylase gene ( PEPCK , EC 4.1.1.49) shows a 1.7‐fold and twofold decrease of TDH protein level and activity, respectively, associated with a 1.8‐fold reduction in threonine‐derived acetate production. We conclude that TDH expression is under control and can be downregulated in response to metabolic perturbations, such as in the PEPCK mutant in which the glycolytic metabolic flux was redirected towards acetate production.