Single amino acid-promoted reactions link a non-enzymatic chemical network to the early evolution of enzymatic pentose phosphate pathway

Publisher PD

Metabolic heterogeneity and cross-feeding within isogenic yeast populations captured by DILAC

Genetically identical cells are known to differ in many physiological parameters such as growth rate and drug tolerance. Metabolic specialization is believed to be a cause of such phenotypic heterogeneity, but detection of metabolically divergent subpopulations remains technically challenging. We developed a proteomics-based technology, termed differential isotope labelling by amino acids (DILAC), that can detect producer and consumer subpopulations of a particular amino acid within an isogenic cell population by monitoring peptides with multiple occurrences of the amino acid. We reveal that young, morphologically undifferentiated yeast colonies contain subpopulations of lysine producers and consumers that emerge due to nutrient gradients. Deconvoluting their proteomes using DILAC, we find evidence for in situ cross-feeding where rapidly growing cells ferment and provide the more slowly growing, respiring cells with ethanol. Finally, by combining DILAC with fluorescence-activated cell sorting, we show that the metabolic subpopulations diverge phenotypically, as exemplified by a different tolerance to the antifungal drug amphotericin B. Overall, DILAC captures previously unnoticed metabolic heterogeneity and provides experimental evidence for the role of metabolic specialization and cross-feeding interactions as a source of phenotypic heterogeneity in isogenic cell populations

Electrocatalytic water oxidation by CuII complexes with branched peptides

Two mononuclear CuII complexes with tetrapeptides incorporating a L-2,3-diaminopropionic acid (dap) branching unit are reported to undergo PCET and catalyse water oxidation. C-terminal His extension of dap (L = 2GH) instead of Gly (L = 3G) lowers the pKa for CuIIIH-2L (9.36 vs. 9.98) and improves the TOF at pH 11 (53 vs. 24 s-1)

Branched peptide with three histidines for the promotion of CuII binding in a wide pH range – complementary potentiometric, spectroscopic and electrochemical studies

Modifications in linear and cyclic peptides have been widely explored in relation with the associated effects on the coordination of CuII. Branching of peptides is yet another innovative conception to promote metal binding. The three dimensional (3D), quasi-tripodal structure of the new ligand, H-His-Dap(H-His)-His-NH2 (3H, where Dap = L-2,3-diaminopropionic acid), which is created by the vicinal two N-terminal and one C-terminal functions of Dap allows triple-arm extension and offers new options in metal binding. A strategy is presented for the characterization of 3H focusing on the role of structural domains in CuII binding by comparison of analogous tetrapeptides that involve a varying number of His and Gly residues. Potentiometric, spectroscopic (UV-Vis, CD and EPR), mass spectrometric and electrochemical data indicate that in monomeric CuII–3H complexes the metal is bound with higher affinity compared to its structural domains indicating that the effect of 3D branching should be taken as an important factor for future studies on CuII peptide constructs

Intramolecular hydrogen bond controlled monodentate S-coordination of N-phosphoryl-N′-(R)-thioureas with Pd(II)

Reaction of N-phosphorylated thioureas RNHC(S)NHP(O)(OiPr)2 (R = tBu, HLI; R = Ph, HLII; R = 4′-benzo-15-crown-5, HLIII) with Pd(PhCN)2Cl2 in acetonitrile leads to complexes of formulae Pd(HLI-S)2Cl2 (1), Pd(HLII-S)2Cl2 (2) and Pd(HLIII-S)2Cl2 (3). The crystal structure of complex 1 has been investigated by X-ray crystallography. It was established that the thiourea ligands are in a trans-configuration and the palladium(II) cation is coordinated by the sulfur atoms of the C{double bond, long}S groups and the chlorine atoms. Complex 1 is the first example of palladium(II) complex in which the potentially chelating N-phosphorylated thiourea ligand is bound through the sulfur atom only. © 2008 Elsevier B.V. All rights reserved

Complexes of N-thiophosphorylthiourea α-naphthylnhc(S)NHP(S)(OiPr)2 (HL) with copper(I). crystal structures of HL and Cu(PPh3)2L

Reaction of the potassium salt of N-thiophosphorylated thiourea α-naphthylNHC(S)NHP(S)(OiPr)2 (HL) with Cu(PPh3)3I in aqueous EtOH/CH2Cl2 leads to the mononuclear complex [Cu(PPh3)2L-S,S′]. By using copper(I) iodide instead of Cu(PPli3)3I, the polynuclear complex [Cun(L-S,S′)n was obtained. The structures of these compounds were investigated by elemental analysis, H and 31P{1H} NMR and IR spectroscopy. The crystal structures of HL and Cu(PPh3)2-L were determined by singlecrystal X-ray diffraction. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA

Monodentate S-vs. bidentate 1,5-O,S-coordination of N-phosphoryl-N′-(R)-thioureas with Pd(II)

Reaction of N-phosphorylated thioureas of common formula RNHC(S)NHP(O)(OiPr)2 (R = tBu, HLI; R = Ph, HLII; R = 4′-benzo-15-crown-5, HLIII) with Pd(PhCN)2Cl2 in acetonitrile leads to complexes of the structure Pd(HLI-S)2Cl2 (1), Pd(HLII-S)2Cl2 (2) and Pd(HLIII-S)2Cl2 (3). Reaction of N-phosphorylated thioureas of common formula RC(S)NHP(O)(OiPr)2 (R = Et2N, HLIV; R = morpholine-N-yl, HLV) in the same conditions leads to complexes Pd(LIV-O,S)2 (4) and Pd(LV-O,S)2 (5), where the palladium(II) atoms are coordinated in a square-planar fashion by the C{double bond, long}S sulfur atoms and the P{double bond, long}O oxygen atoms of two anionic ligands. The crystal structure of complex 1 has been investigated by X-ray crystallography. It was established that the thiourea ligands are in a trans-configuration and the palladium(II) cation is coordinated by the sulfur atoms of the C{double bond, long}S groups and the chlorine atoms. Complex 1 is the first example of palladium(II) complex in which the potentially chelating N-phosphorylated thiourea ligand is bound through the sulfur atom only. © 2008 Elsevier Ltd. All rights reserved

Coordination mode of the nickel(II) cation with N-diisopropoxyphosphinyl-p- bromothiobenzamide

Reaction of the potassium salt of N-diisopropoxyphosphinyl-p- bromothiobenzamide p-BrC6H4C(S)NHP(O)(OiPr)2 (HL) with Ni(NO3)2 in aqueous EtOH leads to complex of formula [Ni(HL-O)2(L-O,S)2] (1). The structure of 1 was investigated by single crystal X-ray diffraction analysis, IR, 1H and 31P{1H} NMR spectroscopy, MALDI and microanalysis. The nickel(II) ion in 1 has a tetragonal-bipyramidal environment, (O ax)2(Oeq)2(Seq) 2, with two neutral ligand molecules coordinated in axial positions through the oxygen atoms of the P=O groups. The equatorial plane of bipyramide is formed by two anionic ligands involving 1,5-O,S-coordination mode. The chelating ligands are bound in trans configuration. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA