Artificial Metalloenzymes in Asymmetric Catalysis: Key Developments and Future Directions

Artificial metalloenzymes combine the excellent selective recognition/binding properties of enzymes with transition metal catalysts, and therefore many asymmetric transformations can benefit from these entities. The search for new successful strategies in the construction of metal-enzyme hybrid catalysts has therefore become a very active area of research. This review discusses all the developed strategies and the latest advances in the synthesis and application in asymmetric catalysis of artificial metalloenzymes with future directions for their design, synthesis and application (Sections 2-4). Finally, advice is presented (to the non-specialist) on how to prepare and use artificial metalloenzymes (Section 5).

[1]  T. Ward,et al.  Biotinylated Metathesis Catalysts: Synthesis and Performance in Ring Closing Metathesis , 2014, Catalysis Letters.

[2]  Jean‐Didier Maréchal,et al.  Structural, kinetic, and docking studies of artificial imine reductases based on biotin-streptavidin technology: an induced lock-and-key hypothesis. , 2014, Journal of the American Chemical Society.

[3]  T. Schirmer,et al.  A dual anchoring strategy for the localization and activation of artificial metalloenzymes based on the biotin-streptavidin technology. , 2013, Journal of the American Chemical Society.

[4]  Jinhua J. Song,et al.  The Growing Impact of Catalysis in the Pharmaceutical Industry , 2011 .

[5]  K. Janda,et al.  A cofactor approach to copper-dependent catalytic antibodies , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. K. Gebbink,et al.  Lipase active site covalent anchoring of Rh(NHC) catalysts: towards chemoselective artificial metalloenzymes. , 2015, Chemical communications.

[7]  Thomas R Ward,et al.  Merging the best of two worlds: artificial metalloenzymes for enantioselective catalysis. , 2011, Chemical communications.

[8]  R. Kazlauskas,et al.  Regioselective Hydroformylation of Styrene Using Rhodium‐Substituted Carbonic Anhydrase , 2010 .

[9]  D. Mathis,et al.  Incorporation of biotinylated manganese-salen complexes into streptavidin : New artificial metalloenzymes for enantioselective sulfoxidation , 2009 .

[10]  J. Tiller,et al.  Polymer Enzyme Conjugates as Chiral Ligands for Sharpless Dihydroxylation of Alkenes in Organic Solvents , 2015, Chembiochem : a European journal of chemical biology.

[11]  M. Salmain,et al.  Enantioselective transfer hydrogenation of ketone catalysed by artificial metalloenzymes derived from bovine β-lactoglobulin. , 2012, Chemical communications.

[12]  J. Fontecilla-Camps,et al.  Artificial metalloenzymes derived from bovine β-lactoglobulin for the asymmetric transfer hydrogenation of an aryl ketone--synthesis, characterization and catalytic activity. , 2014, Dalton transactions.

[13]  T. Ward,et al.  Artificial Metalloenzymes for Enantioselective Catalysis: Recent Advances , 2006, Chembiochem : a European journal of chemical biology.

[14]  Jaiwook Park,et al.  Dynamic Kinetic Resolution of Amines and Amino Acids by Enzyme–Metal Cocatalysis , 2011 .

[15]  A. Mahammed,et al.  Albumin-conjugated corrole metal complexes: extremely simple yet very efficient biomimetic oxidation systems. , 2005, Journal of the American Chemical Society.

[16]  T. Ward,et al.  Improving the enantioselectivity of artificial transfer hydrogenases based on the biotin–streptavidin technology by combinations of point mutations , 2010 .

[17]  T. Ward,et al.  Second Generation Artificial Hydrogenases Based on the Biotin-Avidin Technology: Improving Activity, Stability and Selectivity by Introduction of Enantiopure Amino Acid Spacers , 2007 .

[18]  Thomas R. Ward,et al.  Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C–H Activation , 2012, Science.

[19]  L. Hager,et al.  Highly Enantioselective Propargylic Hydroxylations Catalyzed by Chloroperoxidase , 1999 .

[20]  V. Köhler,et al.  OsO4·streptavidin: a tunable hybrid catalyst for the enantioselective cis-dihydroxylation of olefins. , 2011, Angewandte Chemie.

[21]  Manfred T. Reetz,et al.  Towards the directed evolution of hybrid catalysts , 2002 .

[22]  M. Salmain,et al.  Aqueous phase transfer hydrogenation of aryl ketones catalysed by achiral ruthenium(II) and rhodium(III) complexes and their papain conjugates , 2013 .

[23]  G. Roelfes,et al.  Novel artificial metalloenzymes by in vivo incorporation of metal-binding unnatural amino acids , 2017 .

[24]  Quentin A. Smith,et al.  Mysteries of metals in metalloenzymes. , 2014, Accounts of chemical research.

[25]  George M. Whitesides,et al.  Conversion of a protein to a homogeneous asymmetric hydrogenation catalyst by site-specific modification with a diphosphinerhodium(I) moiety , 1978 .

[26]  D. Hilvert,et al.  An artificial metalloenzyme for olefin metathesis. , 2011, Chemical communications.

[27]  K. Nagayama,et al.  Size-selective olefin hydrogenation by a Pd nanocluster provided in an apo-ferritin cage. , 2004, Angewandte Chemie.

[28]  M. Distefano,et al.  Structural characterization of two synthetic catalysts based on adipocyte lipid-binding protein. , 1998, Protein engineering.

[29]  Peter G Schultz,et al.  A genetically encoded bidentate, metal-binding amino acid. , 2007, Angewandte Chemie.

[30]  E. Dufour,et al.  Probing the fatty acid binding site of β-lactoglobulins , 1993 .

[31]  H. Dijkstra,et al.  Solid-state structural characterization of cutinase-ECE-pincer-metal hybrids. , 2009, Chemistry.

[32]  Andrea Zocchi,et al.  Artificial metalloenzymes for enantioselective catalysis based on biotin-avidin. , 2003, Journal of the American Chemical Society.

[33]  S. Kitagawa,et al.  Mechanism of accumulation and incorporation of organometallic Pd complexes into the protein nanocage of apo-ferritin. , 2010, Inorganic chemistry.

[34]  T. Ward,et al.  Artificial metalloenzymes for asymmetric allylic alkylation on the basis of the biotin-avidin technology. , 2008, Angewandte Chemie.

[35]  B. Jonsson,et al.  Fine tuning of the catalytic properties of carbonic anhydrase. Studies of a Thr200----His variant of human isoenzyme II. , 1990, European journal of biochemistry.

[36]  R. Stenkamp,et al.  X-ray structure and designed evolution of an artificial transfer hydrogenase. , 2008, Angewandte Chemie.

[37]  P. Schultz,et al.  Genetic incorporation of a metal-ion chelating amino acid into proteins as a biophysical probe. , 2009, Journal of the American Chemical Society.

[38]  A. Chan,et al.  Catalytic hydrogenation of itaconic acid in a biotinylated Pyrphos–rhodium(I) system in a protein cavity , 1999 .

[39]  G. Erker,et al.  Control of the coordination structure of organometallic palladium complexes in an apo-ferritin cage. , 2008, Journal of the American Chemical Society.

[40]  J. Fastrez,et al.  Transforming Carbonic Anhydrase into Epoxide Synthase by Metal Exchange , 2006, Chembiochem : a European journal of chemical biology.

[41]  M. Dürrenberger,et al.  Genetic Optimization of the Catalytic Efficiency of Artificial Imine Reductases Based on Biotin–Streptavidin Technology , 2013 .

[42]  B. Höcker,et al.  A Robust Protein Host for Anchoring Chelating Ligands and Organocatalysts , 2008, Chembiochem : a European journal of chemical biology.

[43]  D. Dodds,et al.  Chloroperoxidase-catalyzed asymmetric oxidations: substrate specificity and mechanistic study. , 1995 .

[44]  Patrik Johansson,et al.  X-ray structure of Candida antarctica lipase A shows a novel lid structure and a likely mode of interfacial activation. , 2008, Journal of molecular biology.

[45]  Takashi Yamane,et al.  Coordinated design of cofactor and active site structures in development of new protein catalysts. , 2005, Journal of the American Chemical Society.

[46]  Frank Hollmann,et al.  Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes , 2012, Nature Chemistry.

[47]  Sylwester Mazurek,et al.  Artificial transfer hydrogenases based on the biotin-(strept)avidin technology: fine tuning the selectivity by saturation mutagenesis of the host protein. , 2006, Journal of the American Chemical Society.

[48]  V. Köhler,et al.  Expanding the Chemical Diversity in Artificial Imine Reductases Based on the Biotin–Streptavidin Technology , 2014 .

[49]  M. Novič,et al.  Artificial metalloenzyme for enantioselective sulfoxidation based on vanadyl-loaded streptavidin. , 2008, Journal of the American Chemical Society.

[50]  Frances H. Arnold,et al.  Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes , 2013, Science.

[51]  G. Sanna,et al.  Studies of interaction between Rh(I) and human serum albumin in a "nanostructured biocatalyst" active in the hydroformylation reaction. , 2006, Journal of inorganic biochemistry.

[52]  A. Dexter,et al.  Highly Enantioselective Epoxidation of 1,1-Disubstituted Alkenes Catalyzed by Chloroperoxidase , 1995 .

[53]  F. V. D. Velde,et al.  Enantioselective sulfoxidation mediated by vanadium-incorporated phytase: a hydrolase acting as a peroxidase , 1998 .

[54]  Eishun Tsuchida,et al.  BMC Structural Biology BioMed Central , 2003 .

[55]  A. Zocchi,et al.  Artificial metalloenzymes: (strept)avidin as host for enantioselective hydrogenation by achiral biotinylated rhodium-diphosphine complexes. , 2004, Journal of the American Chemical Society.

[56]  T. Sugimoto,et al.  The bovine serum albumin–2-phenylpropane-1,2-diolatodioxo-somium(VI) complex as an enantioselective catalyst for cis-hydroxylation of alkenes , 1983 .

[57]  M. Blomberg,et al.  Quantum chemical studies of mechanisms for metalloenzymes. , 2014, Chemical reviews.

[58]  Peter G. Schultz,et al.  Biosynthesis of a site-specific DNA cleaving protein. , 2008, Journal of the American Chemical Society.

[59]  M. Distefano,et al.  A Semisynthetic Metalloenzyme Based on a Protein Cavity That Catalyzes the Enantioselective Hydrolysis of Ester and Amide Substrates , 1997 .

[60]  T A Jones,et al.  Crystallization and preliminary X-ray studies of lipase B from Candida antarctica. , 1994, Journal of molecular biology.

[61]  Jean‐Didier Maréchal,et al.  Selective oxidation of aromatic sulfide catalyzed by an artificial metalloenzyme: new activity of hemozymes. , 2009, Organic & biomolecular chemistry.

[62]  S. Colonna,et al.  A new enzymatic enantioselective synthesis of dialkyl sulfoxides catalysed by monooxygenases , 1997 .

[63]  A. Liljas,et al.  Crystallographic analysis of Thr‐200 → His human carbonic anhydrase II and its complex with the substrate, HCO  3− , 1993, Proteins.

[64]  M. Distefano,et al.  Artificial metalloenzymes based on protein cavities: exploring the effect of altering the metal ligand attachment position by site directed mutagenesis. , 1999, Bioorganic & medicinal chemistry letters.

[65]  Jared C. Lewis.  Artificial Metalloenzymes and Metallopeptide Catalysts for Organic Synthesis , 2013 .

[66]  E. Kaiser,et al.  Studies on the oxidase activity of copper(II) carboxypeptidase A , 1976 .

[67]  U. Schwaneberg,et al.  Hybrid ruthenium ROMP catalysts based on an engineered variant of β-barrel protein FhuA ΔCVF(tev) : effect of spacer length. , 2015, Chemistry, an Asian journal.

[68]  Gerard Roelfes,et al.  Enantioselective artificial metalloenzymes by creation of a novel active site at the protein dimer interface. , 2012, Angewandte Chemie.

[69]  François Gilardoni,et al.  Tailoring the active site of chemzymes by using a chemogenetic-optimization procedure: towards substrate-specific artificial hydrogenases based on the biotin-avidin technology. , 2005, Angewandte Chemie.

[70]  A. Heck,et al.  Lipase active-site-directed anchoring of organometallics: metallopincer/protein hybrids. , 2005, Chemistry.

[71]  B. Feringa,et al.  Merging homogeneous catalysis with biocatalysis; papain as hydrogenation catalyst. , 2005, Chemical communications.

[72]  M. Dürrenberger,et al.  Artificial transfer hydrogenases for the enantioselective reduction of cyclic imines. , 2011, Angewandte Chemie.

[73]  A. Slawin,et al.  Artificial Copper Enzymes for Asymmetric Diels–Alder Reactions , 2013 .

[74]  Yi Lu,et al.  A site-selective dual anchoring strategy for artificial metalloprotein design. , 2004, Journal of the American Chemical Society.

[75]  K. Hirata,et al.  Process of accumulation of metal ions on the interior surface of apo-ferritin: crystal structures of a series of apo-ferritins containing variable quantities of Pd(II) ions. , 2009, Journal of the American Chemical Society.

[76]  N. Stephanopoulos,et al.  Choosing an effective protein bioconjugation strategy. , 2011, Nature chemical biology.

[77]  K. Mortensen,et al.  Enantioselective Proteins: Selection, Binding Studies and Molecular Modeling of Antibodies with Affinity towards Hydrophobic BINOL Derivatives , 2007, Chembiochem : a European journal of chemical biology.

[78]  E. Hedaya,et al.  The preparation and reactions of stable phosphorus ylides derived from maleic anhydrides, maleimides or isomaleimides , 1968 .

[79]  T. Ward,et al.  Designed evolution of artificial metalloenzymes: protein catalysts made to order. , 2007, Organic & biomolecular chemistry.

[80]  Takafumi Ueno,et al.  Preparation of artificial metalloenzymes by insertion of chromium(III) Schiff base complexes into apomyoglobin mutants. , 2003, Angewandte Chemie.

[81]  P. Amara,et al.  An artificial oxygenase built from scratch: substrate binding site identified using a docking approach. , 2013, Angewandte Chemie.

[82]  E. Allain,et al.  Highly Enantioselective Epoxidation of Disubstituted Alkenes with Hydrogen Peroxide Catalyzed by Chloroperoxidase. , 1993 .

[83]  Jared C. Lewis,et al.  A General Method for Artificial Metalloenzyme Formation through Strain‐Promoted Azide–Alkyne Cycloaddition , 2014, Chembiochem : a European journal of chemical biology.

[84]  T. Ward,et al.  Chemical optimization of artificial metalloenzymes based on the biotin-avidin technology: (S)-selective and solvent-tolerant hydrogenation catalysts via the introduction of chiral amino acid spacers. , 2005, Chemical communications.

[85]  Tilman Schirmer,et al.  Human Carbonic Anhydrase II as Host Protein for the Creation of Artificial Metalloenzymes : the Asymmetric Transfer Hydrogenation of Imines , 2013 .

[86]  P. Kamer,et al.  Synthesis of hybrid transition-metalloproteins via thiol-selective covalent anchoring of Rh-phosphine and Ru-phenanthroline complexes. , 2010, Dalton transactions.

[87]  Yilin Hu,et al.  Cleaving the n,n triple bond: the transformation of dinitrogen to ammonia by nitrogenases. , 2014, Metal ions in life sciences.

[88]  M. Reetz,et al.  An artificial metalloenzyme: creation of a designed copper binding site in a thermostable protein. , 2010, Angewandte Chemie.

[89]  R. Kazlauskas,et al.  Manganese-substituted carbonic anhydrase as a new peroxidase. , 2006, Chemistry.

[90]  C. Tai,et al.  Co-immobilization of an Enzyme and a Metal into the Compartments of Mesoporous Silica for Cooperative Tandem Catalysis: An Artificial Metalloenzyme , 2013, Angewandte Chemie.

[91]  Gerard Roelfes,et al.  Artificial metalloenzymes for enantioselective catalysis. , 2014, Current opinion in chemical biology.

[92]  H. Levine,et al.  Oxidation of dihydronicotinamides by flavopapain , 1978 .

[93]  G. Roelfes,et al.  An enantioselective artificial metallo-hydratase , 2013 .

[94]  Paul C J Kamer,et al.  Bioinspired catalyst design and artificial metalloenzymes. , 2011, Chemistry.

[95]  A. Willetts,et al.  Asymmetric Sulfoxidation Catalyzed by a Vanadium-Containing Bromoperoxidase. , 1997, The Journal of organic chemistry.

[96]  Thomas R Ward,et al.  Artificial metalloenzymes for olefin metathesis based on the biotin-(strept)avidin technology. , 2011, Chemical communications.

[97]  A. Urvoas,et al.  Incorporation of Manganese Complexes into Xylanase: New Artificial Metalloenzymes for Enantioselective Epoxidation , 2012, Chembiochem : a European journal of chemical biology.

[98]  R. Sheldon,et al.  The rational design of semisynthetic peroxidases. , 2000, Biotechnology and bioengineering.

[99]  B. Martín‐Matute,et al.  Dynamic kinetic resolution catalyzed by enzymes and metals. , 2007, Current opinion in chemical biology.

[100]  Manfred T Reetz,et al.  Directed evolution of hybrid enzymes: Evolving enantioselectivity of an achiral Rh-complex anchored to a protein. , 2006, Chemical communications.

[101]  C. Botting,et al.  Highly efficient and site-selective phosphane modification of proteins through hydrazone linkage: development of artificial metalloenzymes. , 2010, Angewandte Chemie.

[102]  Boi Hoa San,et al.  Platinum nanoparticles encapsulated by aminopeptidase: a multifunctional bioinorganic nanohybrid catalyst. , 2011, Angewandte Chemie.

[103]  K. Ishimori,et al.  Catalytic activities and structural properties of horseradish peroxidase distal His42 --> Glu or Gln mutant. , 1997, Biochemistry.

[104]  H. Schoemaker,et al.  Enantioselective Epoxidation and Carbon–Carbon Bond Cleavage Catalyzed by Coprinus cinereus Peroxidase and Myeloperoxidase* , 2000, The Journal of Biological Chemistry.

[105]  C. Bertucci,et al.  Aqueous Biphasic Hydroformylation Catalysed by Protein-Rhodium Complexes , 2002 .

[106]  M. Marchetti,et al.  A protein–rhodium complex as an efficient catalyst for two-phase olefin hydroformylation , 2000 .

[107]  K. Hirata,et al.  Polymerization of phenylacetylene by rhodium complexes within a discrete space of apo-ferritin. , 2009, Journal of the American Chemical Society.

[108]  M. Morales,et al.  Synthesis of heterogeneous enzyme-metal nanoparticle biohybrids in aqueous media and their applications in C-C bond formation and tandem catalysis. , 2013, Chemical communications.

[109]  D. Lawrence,et al.  Chemical mutation of enzyme active sites. , 1984, Science.

[110]  T. Ward,et al.  Artificial metalloenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[111]  P. Kamer,et al.  Artificial Metalloenzymes through Cysteine‐Selective Conjugation of Phosphines to Photoactive Yellow Protein , 2010, Chembiochem : a European journal of chemical biology.

[112]  B. Vallee,et al.  Metallocarboxypeptidases: stability constants and enzymatic characteristics. , 1961, The Journal of biological chemistry.

[113]  Jean‐Didier Maréchal,et al.  Computational Insights on an Artificial Imine Reductase Based on the Biotin–Streptavidin Technology , 2014 .

[114]  G. Koten,et al.  Non-Tethered Organometallic Phosphonate Inhibitors for Lipase Inhibition: Positioning of the Metal Center in the Active Site of Cutinase , 2008 .

[115]  Jean-Didier Maréchal,et al.  Toward the Computational Design of Artificial Metalloenzymes: From Protein–Ligand Docking to Multiscale Approaches , 2015 .

[116]  R. Kazlauskas,et al.  Stereoselective hydrogenation of olefins using rhodium-substituted carbonic anhydrase--a new reductase. , 2009, Chemistry.

[117]  T. Ward,et al.  Artificial metalloenzymes: proteins as hosts for enantioselective catalysis. , 2005, Chemical Society reviews.

[118]  G. Jaouen,et al.  (Eta6-arene) ruthenium(II) complexes and metallo-papain hybrid as Lewis acid catalysts of Diels-Alder reaction in water. , 2010, Dalton transactions.

[119]  Pilar Hoyos,et al.  Dynamic Kinetic Resolution via Hydrolase‐Metal Combo Catalysis in Stereoselective Synthesis of Bioactive Compounds , 2012 .