Showing papers on "Oxoglutarate dehydrogenase complex published in 2021"

The existence of a nonclassical TCA cycle in the nucleus that wires the metabolic-epigenetic circuitry.

Abstract: The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.

Inhibition of JMJD6 by 2-Oxoglutarate Mimics

Abstract: Studies on the inhibition of the human 2-oxoglutarate dependent oxygenase JMJD6, which is a cancer target, by 2- oxoglutarate mimics / competitors, including human drugs, drug candidates, and metabolites relevant to cancer are described. JMJD6 assays employed NMR to monitor inhibitor binding and use of mass spectrometry to monitor JMJD6 catalysed lysine-hydroxylation. The results will help enable the development of inhibitors selective for human oxygenases, including JMJD6.

Yeast producing ektoin

Abstract: FIELD: ectoine bioproduction.SUBSTANCE: group of inventions relates to the field of ectoine bioproduction. Proposed are recombinant yeast for the production of ectoine, in the genome of which at least one nucleic acid encoding aspartokinase is overexpressed and/or is under the control of an inducible or repressed promoter and/or at least one nucleic acid encoding aspartate kinase is overexpressed and/or is under control of an inducible or repressed promoter. Also, in the genome of said yeast, at least one nucleic acid encoding dehydrogenase of aspartic acid semialdehyde and/or at least one nucleic acid encoding aspartic acid semialdehyde dehydrogenase, which can be used as a coenzyme as nicotinamide adenine dinucleotide (NAD) and nicotinamide (NADP), is overexpressed and/or under the control of an inducible or repressed promoter. Also in the genome of said yeast at least one nucleic acid encoding diaminobutyrate aminotransferase is overexpressed and/or under the control of an inducible or repressed promoter. Also in the genome of said yeast at least one nucleic acid encoding homoserine-O-acetyltransferase METX is overexpressed and/or under the control of an inducible or repressed promoter, and/or at least one nucleic acid encoding diaminobutyric acid acetyltransferase is overexpressed and/or under the control of an inducible or repressible promoter. Also in the genome of said yeast at least one nucleic acid encoding ectoine synthase is overexpressed and/or under the control of an inducible or repressed promoter. Also in the genome of said yeast at least one, preferably all endogenous nucleic acids encoding homoserine dehydrogenase have been removed and/or disrupted, and/or at least one, preferably all nucleic acids encoding homoserine dehydrogenase are independently under the control of an inducible or repressible promoter, under the control of a weak promoter and/or in a destabilized form. Also, in the genome of said yeast, at least one nucleic acid encoding glutamate dehydrogenase using NADH and converting oxoglutarate into glutamate is overexpressed and/or under the control of an inducible or repressed promoter. Also proposed is a method for producing ectoine using said yeast and the use of said yeast for producing ectoine.EFFECT: group of inventions provides highly efficient synthesis and secretion of ectoine.15 cl, 2 ex