Transmembrane NADH Oxidation with Tetracyanoquinodimethane.

The design of efficient schemes for nicotinamide adenine dinucleotide (NAD) regeneration is essential for the development of enzymatic biotechnological processes in order to sustain continuous production. In line with our motivation for the encapsulation of redox cascades in liposomes to serve as microbioreactors, we developed a straightforward strategy for the interfacial oxidation of entrapped NADH by ferricyanide as an external electron acceptor. Instead of the commonly applied enzymatic regeneration methods, we employed a hydrophobic redox shuttle embedded in the liposome bilayer. Tetracyanoquinodimethane (TCNQ) mediated electron transfer across the membrane and thus allowed us to shortcut and emulate part of the electron transfer chain functionality without the involvement of membrane proteins. To describe the experimental system, we developed a mathematical model which allowed for the determination of rate constants and exhibited handy predictive utility.

[1]  S. Fukuzumi,et al.  A mechanistic dichotomy in concerted versus stepwise pathways in hydride and hydrogen transfer reactions of NADH analogues , 2008 .

[2]  L. Lindqvist,et al.  Diphotonic one-electron oxidation of NADH on laser excitation at 353 nm , 1983 .

[3]  K. Sundmacher,et al.  Alternating electron transfer mechanism in the case of high-performance tetrathiafulvalene–tetracyanoquinodimethane enzymatic electrodes , 2013 .

[4]  C. Palivan,et al.  Active surfaces engineered by immobilizing protein-polymer nanoreactors for selectively detecting sugar alcohols. , 2016, Biomaterials.

[5]  Zhongyi Jiang,et al.  Methods for the regeneration of nicotinamide coenzymes , 2013 .

[6]  Daniel A Beard,et al.  Kinetics and regulation of mammalian NADH-ubiquinone oxidoreductase (Complex I). , 2010, Biophysical journal.

[7]  P. Kinnunen,et al.  Quenching of fluorescence of pyrene-substituted lecithin by tetracyanoquinodimethane in liposomes. , 1989, Biophysical journal.

[8]  M. Yoshimoto,et al.  Stability and reactivity of liposome‐encapsulated formate dehydrogenase and cofactor system in carbon dioxide gas‐liquid flow , 2010, Biotechnology progress.

[9]  Tetracyanoquinodimethane-mediated flow injection analysis electrochemical sensor for NADH coupled with dehydrogenase enzymes. , 1994, Analytical biochemistry.

[10]  Vincent Noireaux,et al.  A vesicle bioreactor as a step toward an artificial cell assembly. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Murthy,et al.  NADH sensor with electrochemically modified TCNQ electrode , 1994 .

[12]  P. Hinkle.  A model system for mitochondrial ion transport and respiratory control. , 1970, Biochemical and biophysical research communications.

[13]  R. Leblanc,et al.  Fluorescence properties of plastoquinol, ubiquinol and alpha-tocopherol quinol in solution and liposome membranes. , 1993, Journal of photochemistry and photobiology. B, Biology.

[14]  D. Schiffrin,et al.  A.C. impedance study of rate constants for two-phase electron-transfer reactions , 1993 .

[15]  A. Bard,et al.  Reverse (uphill) electron transfer at the liquid/liquid interface , 1995 .

[16]  Lo Gorton,et al.  Electrocatalytic oxidation of NAD(P) H at mediator-modified electrodes. , 2002, Journal of biotechnology.

[17]  K. Asaka,et al.  Mediated electron transfer across supported bilayer lipid membrane (s-BLM) , 1999 .

[18]  R. van Eldik,et al.  Cation-independent electron transfer between ferricyanide and ferrocyanide ions in aqueous solution. , 2002, Inorganic chemistry.

[19]  K. Edwards,et al.  Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes. , 2015, Biochimica et biophysica acta.

[20]  A. Maesaka,et al.  Bioelectrocatalytic oxidation of glucose with antibiotic channel-containing liposomes. , 2013, Physical chemistry chemical physics : PCCP.

[21]  D. Cole-Hamilton,et al.  Electron transfer across vesicle bilayers , 1991 .

[22]  Oscar Ces,et al.  Vesicle-based artificial cells as chemical microreactors with spatially segregated reaction pathways , 2014, Nature Communications.

[23]  Huimin Zhao,et al.  Recent developments in pyridine nucleotide regeneration. , 2003, Current opinion in biotechnology.

[24]  R. Kataky,et al.  Electron transport in supported and tethered lipid bilayers modified with bioelectroactive molecules. , 2012, The journal of physical chemistry. B.

[25]  J. E. O'Reilly,et al.  Oxidation-reduction potential of the ferro-ferricyanide system in buffer solutions. , 1973, Biochimica et biophysica acta.

[26]  M. Yoshimoto,et al.  Liposomal Encapsulation of Yeast Alcohol Dehydrogenase with Cofactor for Stabilization of the Enzyme Structure and Activity , 2008, Biotechnology progress.

[27]  John A. Nelder,et al.  A Simplex Method for Function Minimization , 1965, Comput. J..

[28]  J. Auwerx,et al.  The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. , 2010, Endocrine reviews.

[29]  A. Bond,et al.  Redox and acid-base chemistry of 7,7,8,8-tetracyanoquinodimethane, 7,7,8,8-tetracyanoquinodimethane radical anion, 7,7,8,8-tetracyanoquinodimethane dianion, and dihydro-7,7,8,8-tetracyanoquinodimethane in acetonitrile. , 2012, Analytical chemistry.

[30]  P. Unwin,et al.  Measurement of the forward and back rate constants for electron transfer at the interface between two immiscible electrolyte solutions using scanning electrochemical microscopy (SECM): Theory and experiment , 2001 .

[31]  C. Soci,et al.  Single photon triggered dianion formation in TCNQ and F4TCNQ crystals , 2016, Scientific Reports.

[32]  R. Marcus,et al.  Electron transfers in chemistry and biology , 1985 .

[33]  P. Sadler,et al.  The Potent Oxidant Anticancer Activity of Organoiridium Catalysts , 2014, Angewandte Chemie.

[34]  Jörg Schaber.  Easy parameter identifiability analysis with COPASI , 2012, Biosyst..

[35]  A. Marcinek,et al.  Direct Observation of NADH Radical Cation Generated in Reactions with One-Electron Oxidants , 2003 .

[36]  R. Ahuja,et al.  Reduction of TCNQ in mixed monolayers with cationic amphiphiles at the air/water interface , 1995 .

[37]  O. Shirai,et al.  Voltammetric study on the electron transport through a bilayer lipid membrane containing neutral or ionic redox molecules , 2003 .

[38]  H. Nakano,et al.  7,7,8,8-Tetracyanoquinodimethane (TCNQ) emits visible photoluminescence in solution , 2017 .

[39]  Mu-Ping Nieh,et al.  Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature. , 2011, Biochimica et biophysica acta.

[40]  L. Kubota,et al.  Study of NADH stability using ultraviolet-visible spectrophotometric analysis and factorial design. , 1998, Analytical biochemistry.

[41]  S. Takeoka,et al.  Reduction of Methemoglobin via Electron Transfer across the Bilayer Membrane of Hb Vesicles , 1997 .

[42]  Yang Li,et al.  Reversible redox of NADH and NAD+ at a hybrid lipid bilayer membrane using ubiquinone. , 2011, Journal of the American Chemical Society.

[43]  P. Neta,et al.  Oxidation of NADH involving rate-limiting one-electron transfer , 1984 .

[44]  O. Shirai,et al.  A liposome-based energy conversion system for accelerating the multi-enzyme reactions. , 2010, Physical chemistry chemical physics : PCCP.

[45]  H. Tien.  715—Cyclic voltammetry of electron-conducting bilayer lipid membranes , 1984 .

[46]  J. Hirst,et al.  The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[47]  M. Ziegler,et al.  The NAD metabolome — a key determinant of cancer cell biology , 2012, Nature Reviews Cancer.

[48]  M. Sangaranarayanan,et al.  Nonequilibrium thermodynamics formalism for Marcus theory of heterogeneous and self-exchange electron-transfer rate constants. , 2008, The journal of physical chemistry. A.

[49]  Freya Q. Schafer,et al.  Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. , 2001, Free radical biology & medicine.

[50]  K. Kontturi,et al.  Potential Dependence of Transmembrane Electron Transfer across Phospholipid Bilayers Mediated by Ubiquinone 10 , 1996 .

[51]  S. Evans,et al.  Driving bioenergetic processes with electrodes , 2011 .

[52]  A. Fontana,et al.  Cardanol as a replacement for cholesterol into the lipid bilayer of POPC liposomes. , 2005, Colloids and surfaces. B, Biointerfaces.

[53]  Thomas Bäck,et al.  An Overview of Evolutionary Algorithms for Parameter Optimization , 1993, Evolutionary Computation.

[54]  Kensuke Kurihara,et al.  Self-reproduction of supramolecular giant vesicles combined with the amplification of encapsulated DNA. , 2011, Nature chemistry.

[55]  P. Wood.  The potential diagram for oxygen at pH 7. , 1988, The Biochemical journal.

[56]  D. Schiffrin,et al.  Redox electrocatalysis by tetracyanoquinodimethane in phospholipid monolayers adsorbed at a liquid/liquid interface , 1994 .

[57]  O. Shirai,et al.  Ion Transport across Planar Bilayer Lipid Membrane Driven by D-Fructose Dehydrogenase-catalyzed Electron Transport , 2011 .

[58]  W. Mahler,et al.  Substituted Quinodimethans. II. Anion-radical Derivatives and Complexes of 7,7,8,8-Tetracyanoquinodimethan , 1962 .

[59]  J. Weinstein,et al.  Carboxyfluorescein leakage assay for lipoprotein-liposome interaction. , 1986, Methods in enzymology.

[60]  L. Guarente,et al.  Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. , 2003, Current opinion in cell biology.

[61]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[62]  P. Schwille.  Bottom-Up Synthetic Biology: Engineering in a Tinkerer’s World , 2011, Science.

[63]  S. Ichikawa,et al.  Enzymes inside lipid vesicles: preparation, reactivity and applications. , 2001, Biomolecular engineering.

[64]  Jingxiang Zhao,et al.  Two-dimensional iron–tetracyanoquinodimethane (Fe–TCNQ) monolayer: an efficient electrocatalyst for the oxygen reduction reaction , 2016 .

[65]  Fabio Mavelli,et al.  Enzymatic reactions in confined environments. , 2016, Nature nanotechnology.