skip to main content
DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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:
1506076
Patent Number(s):
10208322
Application Number:
15/278,561
Assignee:
California Institute of Technology (Pasadena, CA)
Patent Classifications (CPCs):
Y - NEW / CROSS SECTIONAL TECHNOLOGIES Y02 - TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE Y02P - CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
C - CHEMISTRY C12 - BIOCHEMISTRY C12Y - ENZYMES
DOE Contract Number:  
FG02-06ER15762
Resource Type:
Patent
Resource Relation:
Patent File Date: 2016 Sep 28
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES

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., 2019. 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/1506076.
@article{osti_1506076,
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 = {2019},
month = {2}
}

Patent:

Save / Share:

Works referenced in this record:

Catalytic Enantioselective C−H Activation by Means of Metal−Carbenoid-Induced C−H Insertion
journal, August 2003


Engineering Cytochrome P450 BM3 for Terminal Alkane Hydroxylation
journal, April 2006


Phenylalanine 393 Exerts Thermodynamic Control over the Heme of Flavocytochrome P450 BM3
journal, November 2001


Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C-H Activation
journal, October 2012


A Convenient Synthesis of Bifunctional Vicinal Cyclopropanes
journal, January 1978


Enantioselective synthesis of levomilnacipran
journal, January 2012


C-H bond activation in heme proteins: the role of thiolate ligation in cytochrome P450
journal, February 2009


Catalytic Promiscuity in Biocatalysis: Using Old Enzymes to Form New Bonds and Follow New Pathways
journal, November 2004


Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3
journal, June 2009


The role of Thr268 in oxygen activation of cytochrome P450BM-3
journal, November 1995


Scaling and assessment of data quality
journal, December 2005


Iron Porphyrin Catalyzed N−H Insertion Reactions with Ethyl Diazoacetate
journal, July 2007


Basic local alignment search tool
journal, October 1990


Roles of the Proximal Hydrogen Bonding Network in Cytochrome P450 c am -Catalyzed Oxygenation
journal, December 2002


Ruthenium-catalysed carbenoid cyclopropanation reactions with diazo compounds
journal, January 2004


Reaction of carbon tetrachloride with 5,10,15,20-tetraphenyl-porphinatoiron(II)[(TPP)Fe II ]: evidence for the formation of the carbene complex [(TPP)Fe II (CCl2)]
journal, January 1977


(.+-.)-(Z)-2-(Aminomethyl)-1-phenylcyclopropanecarboxamide Derivatives as a New Prototype of NMDA Receptor Antagonists
journal, July 1995


Semisynthesis of axial-ligand (position 80) mutants of cytochrome c
journal, January 1991


Biosynthesis and Metabolism of Cyclopropane Rings in Natural Compounds
journal, April 2003


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010


Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli
journal, September 2010


Highly cis -Selective Cyclopropanations with Ethyl Diazoacetate Using a Novel Rh(I) Catalyst with a Chelating N-Heterocyclic Iminocarbene Ligand
journal, February 2009


Development of a heme protein structure electrochemical function database
journal, December 2007


Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997


Cobalt-Catalyzed Intramolecular C−H Amination with Arylsulfonyl Azides
journal, November 2007


Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins
journal, January 1991


A Self-Sufficient Peroxide-Driven Hydroxylation Biocatalyst
journal, July 2003


Metal-Catalyzed Olefin Cyclopropanation with Ethyl Diazoacetate: Control of the Diastereoselectivity
journal, March 2009


C–H activation
journal, March 2007


Pivotal Role of Water in the Mechanism of P450BM-3
journal, November 2001


The Cytochrome P450 Engineering Database: integration of biochemical properties
journal, January 2009


Stereoselective Cyclopropanation Reactions
journal, April 2003


The role of Thr268 and Phe393 in cytochrome P450 BM3
journal, May 2006


The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies
journal, March 2003


Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates
journal, November 2010


Coot model-building tools for molecular graphics
journal, November 2004


Protein engineering as a tool for understanding electron transfer
journal, August 1993


The Cytochrome P450 Homepage
journal, October 2009


Iron-Catalyzed Cyclopropanation in 6 M KOH with in Situ Generation of Diazomethane
journal, March 2012


Complex reactions catalyzed by cytochrome P450 enzymes
journal, March 2007


The CCP4 suite programs for protein crystallography
journal, September 1994


Recent developments in asymmetric cyclopropanation
journal, July 2008


Integration, scaling, space-group assignment and post-refinement
journal, January 2010


Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion
journal, January 2008


Protein stability promotes evolvability
journal, March 2006


P450-Catalyzed Intramolecular sp 3 C–H Amination with Arylsulfonyl Azide Substrates
journal, December 2013


Probing the molecular determinants of coenzyme selectivity in the P450 BM3 FAD/NADPH domain
journal, August 2009


A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo
journal, June 2013


Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction
journal, July 2010


Insertion of ethyl diazoacetate into N–H and S–H bonds catalyzed by ruthenium porphyrin complexes
journal, January 1997


Well-Defined Binuclear Chiral Spiro Copper Catalysts for Enantioselective N–H Insertion
journal, December 2011


Non-natural Olefin Cyclopropanation Catalyzed by Diverse Cytochrome P450s and Other Hemoproteins
journal, October 2014


Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes
journal, December 2012


SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions
journal, November 2009


Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450
journal, April 2006


Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450BM3 demethylases
journal, September 2009


Dirhodium Tetraprolinate-Catalyzed Asymmetric Cyclopropanations with High Turnover Numbers
journal, May 2003


MOLREP an Automated Program for Molecular Replacement
journal, December 1997


Asymmetric catalytic cyclopropanation reactions in water
journal, March 2008