In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes
Abstract
The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.
- Inventors:
- Issue Date:
- Research Org.:
- California Institute of Technology (CalTech), Pasadena, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1332273
- Patent Number(s):
- 9493799
- Application Number:
- 14/625,449
- Assignee:
- CALIFORNIA INSTITUTE OF TECHNOLOGY (Pasadena, CA)
- Patent Classifications (CPCs):
-
C - CHEMISTRY C12 - BIOCHEMISTRY C12N - MICROORGANISMS OR ENZYMES
C - CHEMISTRY C12 - BIOCHEMISTRY C12P - FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {
- DOE Contract Number:
- FG02-06ER15762
- Resource Type:
- Patent
- Resource Relation:
- Patent File Date: 2015 Feb 18
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Coelho, Pedro S., Brustad, Eric M., Arnold, Frances H., Wang, Zhan, and Lewis, Jared C. In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes. United States: N. p., 2016.
Web.
Coelho, Pedro S., Brustad, Eric M., Arnold, Frances H., Wang, Zhan, & Lewis, Jared C. In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes. United States.
Coelho, Pedro S., Brustad, Eric M., Arnold, Frances H., Wang, Zhan, and Lewis, Jared C. Tue .
"In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes". United States. https://www.osti.gov/servlets/purl/1332273.
@article{osti_1332273,
title = {In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes},
author = {Coelho, Pedro S. and Brustad, Eric M. and Arnold, Frances H. and Wang, Zhan and Lewis, Jared C.},
abstractNote = {The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2016},
month = {11}
}
Works referenced in this record:
Preparation of derivatives of cyclobutane and cyclobutene
patent, June 1976
- Lukas, Joachim H.; Baardman, Frank; Kouwenhoven, Adriaan P.
- US Patent Document 3,965,204
Method of enantioselectively inserting a carbene
patent, March 1994
- Doyle, Michael P.
- US Patent Document 5,296,595
Process for the preparation of an oxirane, azirdine or cyclopropane
patent, December 1997
- Aggarwal, Varinder Kumar; Abdel-Rahman, Hesham Nimer Hasan; Lee, Hee-Yoon
- US Patent Document 5,703,246
Composition comprising methylphenidate and another drug
patent, September 2007
- Richards, Andrew John McGlashan; Pope, Nicholas Robert
- US Patent Document 7,267,949
Borazine-based resin, and method for production thereof, borazine based resin composition, insulating coating and method for formation thereof, and electronic parts having the insulating coating
patent, December 2009
- Matsutani, Hiroshi; Kaji, Makoto; Abe, Koichi
- US Patent Document 7,625,642
Efficient aziridination of olefins catalyzed by dirhodium catalysts
patent, February 2010
- Doyle, Michael P.
- US Patent Document 7,662,969
Regio- and enantioselective alkane hydroxylation with modified cytochrome P450
patent, January 2011
- Arnold, Frances H.; Peters, Matthew W.; Meinhold, Peter
- US Patent Document 7,863,030
Substituted aryl-amine derivatives and methods of use
patent, August 2012
- Yuan, Chester Chenguang
- US Patent Document 8,247,430
In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes
patent, March 2015
- Coelho, Pedro; Brustad, Eric M.; Arnold, Frances H.
- US Patent Document 8,993,262
Cobalt-based catalysts for the cyclization of alkenes
patent-application, February 2006
- Zhang, X. Peter; Chen, Ying; Ruppel, Joshua
- US Patent Application 11/215347; 20060030718
Substituted sulfones and methods of use
patent-application, May 2006
- Askew, JR., Benny C.; Aya, Toshiro; Biswas, Kaustav
- US Patent Application 11/243645; 20060111347
Active Substance Combinations with Insecticidal Properties
patent-application, November 2007
- Eddinghaus, Dirk; Hinterhuber, Andreas; Thielert, Wolfgang
- US Patent Application 10/588616; 20070276013
Compounds and Pharmaceutical Compositions for the Treatment of Viral Infections
patent-application, September 2009
- Sommadossi, Jean-Pierre; Gosselin, Gilles; Pierra, Claire
- US Patent Application 12/005937; 20090238790
C-H Bond Amination and Olefin Aziridination with Beta-Diketiminato Copper Catalysts
patent-application, March 2010
- Warren, Timothy H.
- US Patent Application 12/518189; 20100056806
Method of Producing 6,6Dimethyl-3-Oxabicyclo[3.1.0] Hexan-2-One
patent-application, July 2010
- Hirata, Norihiko; Uemura, Toshitsugi
- US Patent Application 12/091200; 20100168463
Mutant Enzymes
patent-application, September 2010
- Wong, Luet Lok; Bell, Stephen Graham; Whitehouse, Christopher
- US Patent Application 12/681868; 20100240106
Rubber Composition
patent-application, August 2011
- Matsushita, Junko; Ozawa, Yoichi
- US Patent Application 13/122874; 20110196086
Modified Drugs for Use in Liposomal Nanoparticles
patent-application, September 2012
- Cullis, Pieter; Bally, Marcel; Ciufolini, Marco
- US Patent Application 13/467021; 20120237591
P-450-Catalyzed Enantioselective Cyclopropanantion of Electron-Deficient Olefins
patent-application, February 2016
- Renata, Hans; Wang, Z. Jane
- US Patent Application 14/732364; 20160032330
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli
journal, September 2010
- Ajikumar, P. K.; Xiao, W.-H.; Tyo, K. E. J.
- Science, Vol. 330, Issue 6000, p. 70-74
Enantioselective synthesis of levomilnacipran
journal, January 2012
- Alliot, Julien; Gravel, Edmond; Pillon, Florence
- Chemical Communications, Vol. 48, Issue 65
Basic local alignment search tool
journal, October 1990
- Altschul, Stephen F.; Gish, Warren; Miller, Webb
- Journal of Molecular Biology, Vol. 215, Issue 3, p. 403-410
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
Organometallic alkane CH activation
journal, November 2004
- Crabtree, Robert H.
- Journal of Organometallic Chemistry, Vol. 689, Issue 24, p. 4083-4091
Protein stability promotes evolvability
journal, March 2006
- Bloom, J. D.; Labthavikul, S. T.; Otey, C. R.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 15, p. 5869-5874
1-Aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants
journal, February 1987
- Bonnaud, Bernard; Cousse, Henri; Mouzin, Gilbert
- Journal of Medicinal Chemistry, Vol. 30, Issue 2
Catalytic Promiscuity in Biocatalysis: Using Old Enzymes to Form New Bonds and Follow New Pathways
journal, November 2004
- Bornscheuer, Uwe T.; Kazlauskas, Romas J.
- Angewandte Chemie International Edition, Vol. 43, Issue 45, p. 6032-6040
Biomimetic Chemistry: Biology as an Inspiration
journal, September 2008
- Breslow, Ronald
- Journal of Biological Chemistry, Vol. 284, Issue 3
Metal-Catalyzed Olefin Cyclopropanation with Ethyl Diazoacetate: Control of the Diastereoselectivity
journal, March 2009
- Caballero, Ana; Prieto, Auxiliadora; Díaz-Requejo, M. Mar
- European Journal of Inorganic Chemistry, Vol. 2009, Issue 9
A Predictably Selective Aliphatic C H Oxidation Reaction for Complex Molecule Synthesis
journal, November 2007
- Chen, M. S.; White, M. C.
- Science, Vol. 318, Issue 5851
Asymmetric Cyclopropanation of Styrenes Catalyzed by Metal Complexes of D 2 -Symmetrical Chiral Porphyrin: Superiority of Cobalt over Iron
journal, July 2007
- Chen, Ying; Zhang, X. Peter
- The Journal of Organic Chemistry, Vol. 72, Issue 15
A Self‐Sufficient Peroxide‐Driven Hydroxylation Biocatalyst
journal, July 2003
- Cirino, Patrick C.; Arnold, Frances H.
- Angewandte Chemie, Vol. 115, Issue 28, p. 3421-3423
The role of Thr268 and Phe393 in cytochrome P450 BM3
journal, May 2006
- Clark, Jonathan P.; Miles, Caroline S.; Mowat, Christopher G.
- Journal of Inorganic Biochemistry, Vol. 100, Issue 5-6, p. 1075-1090
A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo
journal, June 2013
- Coelho, Pedro S.; Wang, Z. Jane; Ener, Maraia E.
- Nature Chemical Biology, Vol. 9, Issue 8
Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes
journal, December 2012
- Coelho, P. S.; Brustad, E. M.; Kannan, A.
- Science, Vol. 339, Issue 6117
Dirhodium Tetraprolinate-Catalyzed Asymmetric Cyclopropanations with High Turnover Numbers
journal, May 2003
- Davies, Huw M. L.; Venkataramani, Chandrasekar
- Organic Letters, Vol. 5, Issue 9
Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion
journal, January 2008
- Davies, Huw M. L.; Manning, James R.
- Nature, Vol. 451, Issue 7177
Catalytic Enantioselective C−H Activation by Means of Metal−Carbenoid-Induced C−H Insertion
journal, August 2003
- Davies, Huw M. L.; Beckwith, Rohan E. J.
- Chemical Reviews, Vol. 103, Issue 8
Synthesis of cyclopropane containing natural products
journal, October 2001
- Donaldson, William A.
- Tetrahedron, Vol. 57, Issue 41, p. 8589-8627
Dirhodium(II) Tetrakis[methyl 2-oxaazetidine-4-carboxylate]: A Chiral Dirhodium(II) Carboxamidate of Exceptional Reactivity and Selectivity
journal, April 2000
- Doyle, Michael P.; Davies, Simon B.; Hu, Wenhao
- Organic Letters, Vol. 2, Issue 8
Probing the molecular determinants of coenzyme selectivity in the P450 BM3 FAD/NADPH domain
journal, August 2009
- Dunford, Adrian J.; Girvan, Hazel M.; Scrutton, Nigel S.
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1794, Issue 8, p. 1181-1189
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins
journal, January 1991
- Evans, David A.; Woerpel, Keith A.; Hinman, Mira M.
- Journal of the American Chemical Society, Vol. 113, Issue 2, p. 726-728
Scaling and assessment of data quality
journal, December 2005
- Evans, Philip
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
Glutamate–haem ester bond formation is disfavoured in flavocytochrome P450 BM3: characterization of glutamate substitution mutants at the haem site of P450 BM3
journal, April 2010
- Girvan, Hazel M.; Levy, Colin W.; Williams, Paul
- Biochemical Journal, Vol. 427, Issue 3
C-H bond activation in heme proteins: the role of thiolate ligation in cytochrome P450
journal, February 2009
- Green, Michael T.
- Current Opinion in Chemical Biology, Vol. 13, Issue 1, p. 84-88
The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies
journal, March 2003
- Groves, J. T.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 7, p. 3569-3574
Pivotal Role of Water in the Mechanism of P450BM-3 †
journal, November 2001
- Haines, Donovan C.; Tomchick, Diana R.; Machius, Mischa
- Biochemistry, Vol. 40, Issue 45
General Method for Sequence-independent Site-directed Chimeragenesis
journal, July 2003
- Hiraga, Kaori; Arnold, Frances H.
- Journal of Molecular Biology, Vol. 330, Issue 2, p. 287-296
Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C-H Activation
journal, October 2012
- Hyster, T. K.; Knorr, L.; Ward, T. R.
- Science, Vol. 338, Issue 6106
Complex reactions catalyzed by cytochrome P450 enzymes
journal, March 2007
- Isin, Emre M.; Guengerich, F. Peter
- Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1770, Issue 3, p. 314-329
Integration, scaling, space-group assignment and post-refinement
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144
Novel bioreduction system for the production of chiral alcohols
journal, October 2003
- Kataoka, M.; Kita, K.; Wada, M.
- Applied Microbiology and Biotechnology, Vol. 62, Issue 5-6
Stereoselective Cyclopropanation Reactions
journal, April 2003
- Lebel, Hélène; Marcoux, Jean-François; Molinaro, Carmela
- Chemical Reviews, Vol. 103, Issue 4
Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3
journal, June 2009
- Lewis, Jared C.; Arnold, Frances H.
- CHIMIA International Journal for Chemistry, Vol. 63, Issue 6
Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450BM3 demethylases
journal, September 2009
- Lewis, J. C.; Bastian, S.; Bennett, C. S.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 39, p. 16550-16555
Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates
journal, November 2010
- Lewis, Jared C.; Mantovani, Simone M.; Fu, Yu
- ChemBioChem, Vol. 11, Issue 18, p. 2502-2505
Engineering Cytochrome P450 BM3 for Terminal Alkane Hydroxylation
journal, April 2006
- Meinhold, Peter; Peters, Matthew W.; Hartwick, Adam
- Advanced Synthesis & Catalysis, Vol. 348, Issue 6, p. 763-772
Iron-Catalyzed Cyclopropanation in 6 M KOH with in Situ Generation of Diazomethane
journal, March 2012
- Morandi, B.; Carreira, E. M.
- Science, Vol. 335, Issue 6075
A Convenient Synthesis of Bifunctional Vicinal Cyclopropanes
journal, January 1978
- Mouzin, Gilbert; Cousse, Henri; Bonnaud, Bernard
- Synthesis, Vol. 1978, Issue 04
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997
- Murshudov, G. N.; Vagin, A. A.; Dodson, E. J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3
Construction of Catalase Deficient Escherichia coli Strains for the Production of Uricase
journal, January 1996
- Nakagawa, Satoshi; Ishino, Shuichi; Teshiba, Sadao
- Bioscience, Biotechnology, and Biochemistry, Vol. 60, Issue 3
Asymmetric catalytic cyclopropanation reactions in water
journal, March 2008
- Nicolas, Irène; Le Maux, Paul; Simonneaux, Gérard
- Coordination Chemistry Reviews, Vol. 252, Issue 5-7
Phenylalanine 393 Exerts Thermodynamic Control over the Heme of Flavocytochrome P450 BM3 †
journal, November 2001
- Ost, Tobias W. B.; Miles, Caroline S.; Munro, Andrew W.
- Biochemistry, Vol. 40, Issue 45
Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450
journal, April 2006
- Otey, Christopher R.; Landwehr, Marco; Endelman, Jeffrey B.
- PLoS Biology, Vol. 4, Issue 5
Recent developments in asymmetric cyclopropanation
journal, July 2008
- Pellissier, Hélène
- Tetrahedron, Vol. 64, Issue 30-31, p. 7041-7095
Cyclopropanation of Olefins with Diazoalkanes, Catalyzed by CoII(porphyrin) Complexes − A Synthetic and Mechanistic Investigation and the Molecular Structure of CoIII(TPP)(CH2CO2Et) (TPP = Dianion of meso-Tetraphenylporphyrin)
journal, April 2003
- Penoni, Andrea; Wanke, Riccardo; Tollari, Stefano
- European Journal of Inorganic Chemistry, Vol. 2003, Issue 7
Molecular basis for the inability of an oxygen atom donor ligand to replace the natural sulfur donor heme axial ligand in cytochrome P450 catalysis. Spectroscopic characterization of the Cys436Ser CYP2B4 mutant
journal, March 2011
- Perera, Roshan; Sono, Masanori; Voegtle, Heather L.
- Archives of Biochemistry and Biophysics, Vol. 507, Issue 1, p. 119-125
SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions
journal, November 2009
- Preissner, Saskia; Kroll, Katharina; Dunkel, Mathias
- Nucleic Acids Research, Vol. 38, Issue suppl_1
Semisynthesis of axial-ligand (position 80) mutants of cytochrome c
journal, January 1991
- Raphael, Adrienne L.; Gray, Harry B.
- Journal of the American Chemical Society, Vol. 113, Issue 3, p. 1038-1040
Development of a heme protein structure electrochemical function database
journal, December 2007
- Reedy, C. J.; Elvekrog, M. M.; Gibney, B. R.
- Nucleic Acids Research, Vol. 36, Issue Database
Highly cis -Selective Cyclopropanations with Ethyl Diazoacetate Using a Novel Rh(I) Catalyst with a Chelating N-Heterocyclic Iminocarbene Ligand
journal, February 2009
- Rosenberg, Marianne Lenes; Krivokapic, Alexander; Tilset, Mats
- Organic Letters, Vol. 11, Issue 3
Cobalt-Catalyzed Intramolecular C−H Amination with Arylsulfonyl Azides
journal, November 2007
- Ruppel, Joshua V.; Kamble, Rajesh M.; Zhang, X. Peter
- Organic Letters, Vol. 9, Issue 23
Catalyst structure and the enantioselective cyclopropanation of alkenes by copper complexes of biaryldiimines: the importance of ligand acceleration
journal, May 2001
- Sanders, Christopher J.; Gillespie, Kevin M.; Scott, Peter
- Tetrahedron: Asymmetry, Vol. 12, Issue 7, p. 1055-1061
(.+-.)-(Z)-2-(Aminomethyl)-1-phenylcyclopropanecarboxamide Derivatives as a New Prototype of NMDA Receptor Antagonists
journal, July 1995
- Shuto, Satoshi; Takada, Hironao; Mochizuki, Daisuke
- Journal of Medicinal Chemistry, Vol. 38, Issue 15
Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction
journal, July 2010
- Siegel, J. B.; Zanghellini, A.; Lovick, H. M.
- Science, Vol. 329, Issue 5989
The Cytochrome P450 Engineering Database: integration of biochemical properties
journal, January 2009
- Sirim, Demet; Wagner, Florian; Lisitsa, Andrey
- BMC Biochemistry, Vol. 10, Issue 1
MOLREP an Automated Program for Molecular Replacement
journal, December 1997
- Vagin, A.; Teplyakov, A.
- Journal of Applied Crystallography, Vol. 30, Issue 6, p. 1022-1025
Replacement of active-site cysteine-436 by serine converts cytochrome P450 2B4 into an NADPH oxidase with negligible monooxygenase activity
journal, September 2002
- Vatsis, Kostas P.; Peng, Hwei-Ming; Coon, Minor J.
- Journal of Inorganic Biochemistry, Vol. 91, Issue 4, p. 542-553
Biosynthesis and Metabolism of Cyclopropane Rings in Natural Compounds
journal, April 2003
- Wessjohann, Ludger A.; Brandt, Wolfgang; Thiemann, Thies
- Chemical Reviews, Vol. 103, Issue 4
Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin
journal, January 2012
- Westfall, P. J.; Pitera, D. J.; Lenihan, J. R.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 3, p. E111-E118
Shape and stereoselective cyclopropanation of alkenes catalyzed by iron porphyrins.
journal, September 1995
- Wolf, Jennifer Robbins; Hamaker, Christopher G.; Djukic, Jean-Pierre
- Journal of the American Chemical Society, Vol. 117, Issue 36
Protein engineering as a tool for understanding electron transfer
journal, August 1993
- Wuttke, Deborah S.; Gray, Harry B.
- Current Opinion in Structural Biology, Vol. 3, Issue 4, p. 555-563
The role of Thr268 in oxygen activation of cytochrome P450BM-3
journal, November 1995
- Yeom, Hyeyeong; Sligar, Stephen G.; Li, Huiying
- Biochemistry, Vol. 34, Issue 45
Roles of the Proximal Hydrogen Bonding Network in Cytochrome P450 c am -Catalyzed Oxygenation
journal, December 2002
- Yoshioka, Shiro; Tosha, Takehiko; Takahashi, Satoshi
- Journal of the American Chemical Society, Vol. 124, Issue 49
BuMgNiPr2: A New Base for Stoichiometric, Position-Selective Deprotonation of Cyclopropane Carboxamides and Other Weak CH Acids
journal, June 2002
- Zhang, Mao-Xi; Eaton, Philip E.
- Angewandte Chemie, Vol. 114, Issue 12, p. 2273–2275