Myxobacteria feature unique biological characteristics including their capability to glide on surface, undergo different multicellular developmental stages and produce structurally unique natural products such as the catecholate-type siderophores myxochelin A and B. Herein, we report the isolation, structure elucidation and biosynthesis of the new congener myxochelin B-succinate from the terrestrial myxobacterial strain MSr12020, featuring a succinyl decoration at its primary amine group. Myxochelin-B-succinate exhibited antifungal growth inhibition and moderate cytotoxic activity against selected human cancer cell lines. This unique chemical modification of myxochelin B might provide interesting insights for future microbiological studies to understand the biological function and biosynthesis of secondary metabolite succinylation.

Mitochondrial pyruvate dehydrogenase complex (PDHC) is essential for the brain glucose and neurotransmitter metabolism, dysregulated in many pathologies. Using specific inhibitors of PDHC in vivo, we determine biochemical and physiological responses to PDHC dysfunction. Dose dependence of the responses to membrane-permeable dimethyl acetylphosphonate (Ac-PMe2) is non-monotonous. Primary decreases in glutathione and its redox potential, methionine and ethanolamine are alleviated with increasing PDHC inhibition, the alleviation accompanied by physiological changes. Comparison of 39 brain biochemical parameters after administration of four phosphinate and phosphonate analogs of pyruvate at a fixed dose of 0.1 mmol/kg reveals no primary, but the secondary changes, such as activation of 2-oxoglutarate dehydrogenase complex (OGDHC) and decreased levels of glutamate, isoleucine and leucine. The accompanying decreases in RMSSD of ECG and freezing time are most pronounced after administration of me-thyl acetylphosphinate and dimethyl acetylphosphonate. The levels of PDHA1 expression and phosphorylation, sirtuin 3 and total protein acetylation are not significantly changed by the PDHC inhibitors that affect the brain protein succinylation and glutarylation. Thus, decreased production of the tricarboxylic acid cycle substrate acetyl-CoA by inhibited PDHC is compen-sated by increased degradation of amino acids through the cycle with activated OGDHC, increas-ing total protein succinylation and decreasing anxiety indicators.