Overcoming co-product inhibition in the nicotinamide independent asymmetric bioreduction of activated C=C-bonds using flavin-dependent ene-reductases

Eleven flavoproteins from the old yellow enzyme family were found to catalyze the disproportionation (“dismutation”) of conjugated enones. Incomplete conversions, which were attributed to enzyme inhibition by the co‐product phenol could be circumvented via in situ co‐product removal by scavenging the phenol using the polymeric adsorbent MP‐carbonate. The optimized system allowed to reduce an alkene activated by ester groups in a “coupled‐substrate” approach via nicotinamide‐free hydrogen transfer with >90% conversion and complete stereoselectivity. Biotechnol. Bioeng. 2013;110: 3085–3092. © 2013 The Authors. Biotechnology and Bioengineering Published by Willey Periodicals, Inc.

[1]  S. Chakraborty,et al.  Old Yellow enzyme: aromatization of cyclic enones and the mechanism of a novel dismutation reaction. , 1995, Biochemistry.

[2]  G. Bourenkov,et al.  The 1.3 Å Crystal Structure of the Flavoprotein YqjM Reveals a Novel Class of Old Yellow Enzymes* , 2005, Journal of Biological Chemistry.

[3]  R. Stewart,et al.  Potentiometric studies of native and flavin-substituted Old Yellow Enzyme. , 1985, The Journal of biological chemistry.

[4]  R. Matthews,et al.  Identification of p-hydroxybenzaldehyde as the ligand in the green form of old yellow enzyme. , 1975, Journal of Biological Chemistry.

[5]  S. Miller,et al.  Binding and reactivity of Candida albicans estrogen binding protein with steroid and other substrates. , 1998, Biochemistry.

[6]  Bernhard Hauer,et al.  Asymmetric bioreduction of activated C=C bonds using enoate reductases from the old yellow enzyme family. , 2007, Current opinion in chemical biology.

[7]  A. Bommarius,et al.  Asymmetric bioreduction of alkenes using ene-reductases YersER and KYE1 and effects of organic solvents. , 2011, Organic letters.

[8]  V. Massey,et al.  Purification of intact old yellow enzyme using an affinity matrix for the sole chromatographic step. , 1976, The Journal of biological chemistry.

[9]  Michael A. Lyon,et al.  Glyoxylic acid and MP-glyoxylate: efficient formaldehyde equivalents in the 3-CC of 2-aminoazines, aldehydes, and isonitriles. , 2004, Organic letters.

[10]  Frank Hollmann,et al.  Biocatalytic Redox Reactions for Organic Synthesis: Nonconventional Regeneration Methods , 2010 .

[11]  Bernhard Hauer,et al.  The Substrate Spectra of Pentaerythritol Tetranitrate Reductase, Morphinone Reductase, N‐Ethylmaleimide Reductase and Estrogen‐Binding Protein in the Asymmetric Bioreduction of Activated Alkenes , 2010 .

[12]  F. Dickert,et al.  Cysteine as a modulator residue in the active site of xenobiotic reductase A: a structural, thermodynamic and kinetic study. , 2010, Journal of Molecular Biology.

[13]  I. Jelesarov,et al.  Characterization of a thermostable NADPH:FMN oxidoreductase from the mesophilic bacterium Bacillus subtilis. , 2006, Biochemistry.

[14]  M. Schittmayer,et al.  Old Yellow Enzyme-Catalyzed Dehydrogenation of Saturated Ketones , 2011 .

[15]  B. Hauer,et al.  Asymmetric Bioreduction of Activated C=C Bonds Using Zymomonas mobilis NCR Enoate Reductase and Old Yellow Enzymes OYE 1–3 from Yeasts , 2008 .

[16]  D. Sell,et al.  Production of 2-phenylethanol and 2-phenylethylacetate from L-phenylalanine by coupling whole-cell biocatalysis with organophilic pervaporation. , 2005, Biotechnology and bioengineering.

[17]  A. Bommarius,et al.  Hydrogen peroxide-producing NADH oxidase (nox-1) from Lactococcus lactis , 2004 .

[18]  T. Matsuda,et al.  Recent Progress in Biocatalysis for Asymmetric Oxidation and Reduction , 2009 .

[19]  G J Lye,et al.  Application of in situ product-removal techniques to biocatalytic processes. , 1999, Trends in biotechnology.

[20]  A. Bommarius,et al.  Cofactor Regeneration of NAD+ from NADH: Novel Water-Forming NADH Oxidases , 2002 .

[21]  G. Tasnádi,et al.  Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds , 2012, Journal of biotechnology.

[22]  E. Weitz,et al.  Umwandlungen der Ketoxidoverbindungen; Bildung von β-Keto-aldehyden aus α,β-ungesättigten Ketonen , 1921 .

[23]  N. Scrutton,et al.  Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation. , 2009, Advanced synthesis & catalysis.

[24]  K. Gruber,et al.  Structure and function of YcnD from Bacillus subtilis, a flavin-containing oxidoreductase. , 2005, Biochemistry.

[25]  P. Macheroux,et al.  A Homolog of Old Yellow Enzyme in Tomato , 1999, The Journal of Biological Chemistry.

[26]  C. Wandrey Biochemical reaction engineering for redox reactions. , 2004, Chemical record.

[27]  P. Macheroux,et al.  Stereocomplementary bioreduction of alpha,beta-unsaturated dicarboxylic acids and dimethyl esters using enoate reductases: enzyme- and substrate-based stereocontrol. , 2007, Organic letters.

[28]  G. Daum,et al.  Lot6p from Saccharomyces cerevisiae is a FMN‐dependent reductase with a potential role in quinone detoxification , 2007, The FEBS journal.

[29]  B. Hauer,et al.  Asymmetric alkene reduction by yeast old yellow enzymes and by a novel Zymomonas mobilis reductase , 2007, Biotechnology and bioengineering.

[30]  I. Arends,et al.  Photoenzymatic Reduction of CC Double Bonds , 2009 .

[31]  B. Sewell,et al.  Crystal structure of a thermostable old yellow enzyme from Thermus scotoductus SA-01. , 2010, Biochemical and biophysical research communications.

[32]  Frank Hollmann,et al.  Mimicking nature: synthetic nicotinamide cofactors for C═C bioreduction using enoate reductases. , 2013, Organic letters.

[33]  A. Bommarius,et al.  Nitroreductase from Salmonella typhimurium: characterization and catalytic activity. , 2010, Organic & biomolecular chemistry.

[34]  P. Karplus,et al.  Structure‐function relations for old yellow enzyme , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  Wolfgang Kroutil,et al.  A highly efficient ADH-coupled NADH-recycling system for the asymmetric bioreduction of carbon-carbon double bonds using enoate reductases. , 2011, Biotechnology and bioengineering.

[36]  H. Ohta,et al.  Purification and characterization of thermostable H2O2-forming NADH oxidase from 2-phenylethanol-assimilating Brevibacterium sp. KU1309 , 2008, Applied Microbiology and Biotechnology.

[37]  D. Opperman,et al.  A Novel Chromate Reductase from Thermus scotoductus SA-01 Related to Old Yellow Enzyme , 2008, Journal of bacteriology.

[38]  M. Reetz,et al.  Light‐Driven Biocatalytic Oxidation and Reduction Reactions: Scope and Limitations , 2008, Chembiochem : a European journal of chemical biology.

[39]  V. Massey,et al.  Interaction of phenols with old yellow enzyme. Physical evidence for charge-transfer complexes. , 1976, The Journal of biological chemistry.

[40]  Urs von Stockar,et al.  In situ product removal (ISPR) in whole cell biotechnology during the last twenty years. , 2003, Advances in biochemical engineering/biotechnology.

[41]  S. M. Glueck,et al.  The flavoprotein-catalyzed reduction of aliphatic nitro-compounds represents a biocatalytic equivalent to the Nef-reaction , 2010 .

[42]  K. Faber,et al.  Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases , 2013, The Journal of organic chemistry.

[43]  P. Macheroux,et al.  Epoxidation of conjugated C=C-bonds and sulfur-oxidation of thioethers mediated by NADH:FMN-dependent oxidoreductases. , 2009, Organic & biomolecular chemistry.

[44]  N. Scrutton,et al.  Biocatalytic Reductions and Chemical Versatility of the Old Yellow Enzyme Family of Flavoprotein Oxidoreductases , 2010 .

[45]  Nina Baudendistel,et al.  Nicotinamide-independent asymmetric bioreduction of CC-bonds via disproportionation of enones catalyzed by enoate reductases. , 2010, Tetrahedron.

[46]  R. Huber,et al.  Crystal structure of 12-oxophytodienoate reductase 3 from tomato: Self-inhibition by dimerization , 2006, Proceedings of the National Academy of Sciences.

[47]  A. Bommarius,et al.  Characterization of xenobiotic reductase A (XenA): study of active site residues, substrate spectrum and stability. , 2010, Chemical communications.

[48]  P. Macheroux,et al.  Asymmetric bioreduction of activated alkenes using cloned 12-oxophytodienoate reductase isoenzymes OPR-1 and OPR-3 from Lycopersicon esculentum (tomato): a striking change of stereoselectivity. , 2007, Angewandte Chemie.

[49]  S. Miller,et al.  Transient kinetics and intermediates formed during the electron transfer reaction catalyzed by Candida albicans estrogen binding protein. , 2000, Biochemistry.