Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor

Gu, Yang; Natoli, Sean N.; Liu, Zhennan; Clark, Douglas S.; Hartwig, John F.

doi:10.1002/anie.201907460

Site-Selective Functionalization of (sp³)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor

Journal Article · Mon Sep 23 04:00:00 EDT 2019 · Angewandte Chemie (International Edition)

DOI:https://doi.org/10.1002/anie.201907460· OSTI ID:1633240

Gu, Yang ^[1]; Natoli, Sean N. ^[1]; Liu, Zhennan ^[1]; Clark, Douglas S. ^[1]; ^[1]

Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

The selective functionalization of one C-H bond over others in nearly identical steric and electronic environments can facilitate the construction of complex molecules. We report site-selective functionalizations of C-H bonds, differentiated solely by remote substituents, catalyzed by artificial metalloenzymes (ArMs) that are generated from the combination of an evolvable P450 scaffold and an iridium-porphyrin cofactor. The generated systems catalyze the insertion of carbenes into the C-H bonds of a range of phthalan derivatives containing substituents that render the two methylene positions in each phthalan inequivalent. These reactions occur with site-selectivity ratios of up to 17.8:1 and, in most cases, with pairs of enzyme mutants that preferentially form each of the two constitutional isomers. This study demonstrates the potential of abiotic reactions catalyzed by metalloenzymes to functionalize C-H bonds with site selectivity that is difficult to achieve with small-molecule catalysts.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1633240

Alternate ID(s):: OSTI ID: 1558124

Journal Information:: Angewandte Chemie (International Edition), Journal Name: Angewandte Chemie (International Edition) Journal Issue: 39 Vol. 58; ISSN 1521-3773; ISSN 1433-7851

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

Metal Substitution Modulates the Reactivity and Extends the Reaction Scope of Myoglobin Carbene Transfer Catalysts Sreenilayam, Gopeekrishnan; Moore, Eric J.; Steck, Viktoria Advanced Synthesis & Catalysis, Vol. 359, Issue 12 https://doi.org/10.1002/adsc.201700202	journal	May 2017
Funktionalisierung von C-H-Bindungen: neue Synthesemethoden für Naturstoffe und Pharmazeutika Yamaguchi, Junichiro; Yamaguchi, Atsushi D.; Itami, Kenichiro Angewandte Chemie, Vol. 124, Issue 36 https://doi.org/10.1002/ange.201201666	journal	August 2012
Gerichtete Evolution: Wie man neue Chemie zum Leben erweckt Arnold, Frances H. Angewandte Chemie, Vol. 130, Issue 16 https://doi.org/10.1002/ange.201708408	journal	November 2017
Preparation of Artificial Metalloenzymes by Insertion of Chromium(III) Schiff Base Complexes into Apomyoglobin Mutants Ohashi, Masataka; Koshiyama, Tomomi; Ueno, Takafumi Angewandte Chemie International Edition, Vol. 42, Issue 9 https://doi.org/10.1002/anie.200390256	journal	March 2003
CH Bond Functionalization: Emerging Synthetic Tools for Natural Products and Pharmaceuticals Yamaguchi, Junichiro; Yamaguchi, Atsushi D.; Itami, Kenichiro Angewandte Chemie International Edition, Vol. 51, Issue 36 https://doi.org/10.1002/anie.201201666	journal	August 2012
Directed Evolution: Bringing New Chemistry to Life Arnold, Frances H. Angewandte Chemie International Edition, Vol. 57, Issue 16 https://doi.org/10.1002/anie.201708408	journal	November 2017
New Concepts for Increasing the Efficiency in Directed Evolution of Stereoselective Enzymes Sun, Zhoutong; Wikmark, Ylva; Bäckvall, Jan-E. Chemistry - A European Journal, Vol. 22, Issue 15 https://doi.org/10.1002/chem.201504406	journal	February 2016
Ratio of ellipticities between 192 and 208 nm ( R ₁ ): An effective electronic circular dichroism parameter for characterization of the helical components of proteins and peptides Banerjee, Raja; Sheet, Tridip Proteins: Structure, Function, and Bioinformatics, Vol. 85, Issue 11 https://doi.org/10.1002/prot.25351	journal	August 2017
Complex reactions catalyzed by cytochrome P450 enzymes Isin, Emre M.; Guengerich, F. Peter Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1770, Issue 3, p. 314-329 https://doi.org/10.1016/j.bbagen.2006.07.003	journal	March 2007
Metallopeptide catalysts and artificial metalloenzymes containing unnatural amino acids Lewis, Jared C. Current Opinion in Chemical Biology, Vol. 25 https://doi.org/10.1016/j.cbpa.2014.12.016	journal	April 2015
Design and evolution of enzymes for non-natural chemistry Hammer, Stephan C.; Knight, Anders M.; Arnold, Frances H. Current Opinion in Green and Sustainable Chemistry, Vol. 7 https://doi.org/10.1016/j.cogsc.2017.06.002	journal	October 2017
Exploiting and engineering hemoproteins for abiological carbene and nitrene transfer reactions Brandenberg, Oliver F.; Fasan, Rudi; Arnold, Frances H. Current Opinion in Biotechnology, Vol. 47 https://doi.org/10.1016/j.copbio.2017.06.005	journal	October 2017
Artificial Metalloenzymes Based on the Biotin–Streptavidin Technology: Challenges and Opportunities Heinisch, Tillmann; Ward, Thomas R. Accounts of Chemical Research, Vol. 49, Issue 9 https://doi.org/10.1021/acs.accounts.6b00235	journal	August 2016
Peptide-Based Catalysts Reach the Outer Sphere through Remote Desymmetrization and Atroposelectivity Metrano, Anthony J.; Miller, Scott J. Accounts of Chemical Research, Vol. 52, Issue 1 https://doi.org/10.1021/acs.accounts.8b00473	journal	December 2018
Directed Evolution of Artificial Metalloenzymes: A Universal Means to Tune the Selectivity of Transition Metal Catalysts? Reetz, Manfred T. Accounts of Chemical Research, Vol. 52, Issue 2 https://doi.org/10.1021/acs.accounts.8b00582	journal	January 2019
Noble−Metal Substitution in Hemoproteins: An Emerging Strategy for Abiological Catalysis Natoli, Sean N.; Hartwig, John F. Accounts of Chemical Research, Vol. 52, Issue 2 https://doi.org/10.1021/acs.accounts.8b00586	journal	January 2019
Artificial Metalloenzymes Based on the Biotin–Streptavidin Technology: Enzymatic Cascades and Directed Evolution Liang, Alexandria Deliz; Serrano-Plana, Joan; Peterson, Ryan L. Accounts of Chemical Research, Vol. 52, Issue 3 https://doi.org/10.1021/acs.accounts.8b00618	journal	February 2019
Beyond the Second Coordination Sphere: Engineering Dirhodium Artificial Metalloenzymes To Enable Protein Control of Transition Metal Catalysis Lewis, Jared C. Accounts of Chemical Research, Vol. 52, Issue 3 https://doi.org/10.1021/acs.accounts.8b00625	journal	March 2019
Understanding and Modulating Metalloenzymes with Unnatural Amino Acids, Non-Native Metal Ions, and Non-Native Metallocofactors Mirts, Evan N.; Bhagi-Damodaran, Ambika; Lu, Yi Accounts of Chemical Research, Vol. 52, Issue 4 https://doi.org/10.1021/acs.accounts.9b00011	journal	March 2019
Artificial Metalloenzymes: Reaction Scope and Optimization Strategies Schwizer, Fabian; Okamoto, Yasunori; Heinisch, Tillmann Chemical Reviews, Vol. 118, Issue 1 https://doi.org/10.1021/acs.chemrev.7b00014	journal	May 2017
Engineering of RuMb: Toward a Green Catalyst for Carbene Insertion Reactions Wolf, Matthew W.; Vargas, David A.; Lehnert, Nicolai Inorganic Chemistry, Vol. 56, Issue 10 https://doi.org/10.1021/acs.inorgchem.6b03148	journal	April 2017
Reactivity Comparison of Primary Aromatic Amines and Thiols in E–H Insertion Reactions with Diazoacetates Catalyzed by Iridium(III) Tetratolylporphyrin Anding, Bernie J.; Dairo, Taiwo O.; Woo, L. Keith Organometallics, Vol. 36, Issue 9 https://doi.org/10.1021/acs.organomet.7b00185	journal	April 2017
Site-Selective Carbene-Induced C–H Functionalization Catalyzed by Dirhodium Tetrakis(triarylcyclopropanecarboxylate) Complexes Liao, Kuangbiao; Liu, Wenbin; Niemeyer, Zachary L. ACS Catalysis, Vol. 8, Issue 1 https://doi.org/10.1021/acscatal.7b03421	journal	December 2017
Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes Key, Hanna M.; Dydio, Paweł; Liu, Zhennan ACS Central Science, Vol. 3, Issue 4 https://doi.org/10.1021/acscentsci.6b00391	journal	April 2017
Weak Coordination as a Powerful Means for Developing Broadly Useful C–H Functionalization Reactions Engle, Keary M.; Mei, Tian-Sheng; Wasa, Masayuki Accounts of Chemical Research, Vol. 45, Issue 6 https://doi.org/10.1021/ar200185g	journal	December 2011
Innate and Guided C–H Functionalization Logic Brückl, Tobias; Baxter, Ryan D.; Ishihara, Yoshihiro Accounts of Chemical Research, Vol. 45, Issue 6 https://doi.org/10.1021/ar200194b	journal	October 2011
A survey of Hammett substituent constants and resonance and field parameters Hansch, Corwin.; Leo, A.; Taft, R. W. Chemical Reviews, Vol. 91, Issue 2 https://doi.org/10.1021/cr00002a004	journal	March 1991
Catalytic Carbene Insertion into C−H Bonds Doyle, Michael P.; Duffy, Richard; Ratnikov, Maxim Chemical Reviews, Vol. 110, Issue 2 https://doi.org/10.1021/cr900239n	journal	February 2010
Intermolecular Copper-Catalyzed Carbon−Hydrogen Bond Activation via Carbene Insertion Díaz-Requejo, M. Mar; Belderraín, Tomás R.; Nicasio, M. Carmen Journal of the American Chemical Society, Vol. 124, Issue 6 https://doi.org/10.1021/ja016798j	journal	February 2002
A Site-Selective Dual Anchoring Strategy for Artificial Metalloprotein Design Carey, James R.; Ma, Steven K.; Pfister, Thomas D. Journal of the American Chemical Society, Vol. 126, Issue 35 https://doi.org/10.1021/ja046908x	journal	September 2004
Directing Group-Controlled Regioselectivity in an Enzymatic C–H Bond Oxygenation Negretti, Solymar; Narayan, Alison R. H.; Chiou, Karoline C. Journal of the American Chemical Society, Vol. 136, Issue 13 https://doi.org/10.1021/ja5016052	journal	March 2014
Evolution of C–H Bond Functionalization from Methane to Methodology Hartwig, John F. Journal of the American Chemical Society, Vol. 138, Issue 1 https://doi.org/10.1021/jacs.5b08707	journal	December 2015
Identification of Mechanism-Based Inactivation in P450-Catalyzed Cyclopropanation Facilitates Engineering of Improved Enzymes Renata, Hans; Lewis, Russell D.; Sweredoski, Michael J. Journal of the American Chemical Society, Vol. 138, Issue 38 https://doi.org/10.1021/jacs.6b06823	journal	September 2016
Chemoselective, Enzymatic C–H Bond Amination Catalyzed by a Cytochrome P450 Containing an Ir(Me)-PIX Cofactor Dydio, Paweł; Key, Hanna M.; Hayashi, Hiroki Journal of the American Chemical Society, Vol. 139, Issue 5 https://doi.org/10.1021/jacs.6b11410	journal	January 2017
Catalytic Cyclopropanation by Myoglobin Reconstituted with Iron Porphycene: Acceleration of Catalysis due to Rapid Formation of the Carbene Species Oohora, Koji; Meichin, Hiroyuki; Zhao, Liming Journal of the American Chemical Society, Vol. 139, Issue 48 https://doi.org/10.1021/jacs.7b10154	journal	November 2017
Directed Evolution of a Cytochrome P450 Carbene Transferase for Selective Functionalization of Cyclic Compounds Brandenberg, Oliver F.; Chen, Kai; Arnold, Frances H. Journal of the American Chemical Society, Vol. 141, Issue 22 https://doi.org/10.1021/jacs.9b02931	journal	May 2019
Site-selective and stereoselective functionalization of unactivated C–H bonds Liao, Kuangbiao; Negretti, Solymar; Musaev, Djamaladdin G. Nature, Vol. 533, Issue 7602 https://doi.org/10.1038/nature17651	journal	May 2016
Abiological catalysis by artificial haem proteins containing noble metals in place of iron Key, Hanna M.; Dydio, Paweł; Clark, Douglas S. Nature, Vol. 534, Issue 7608 https://doi.org/10.1038/nature17968	journal	June 2016
Site-selective and stereoselective functionalization of non-activated tertiary C–H bonds Liao, Kuangbiao; Pickel, Thomas C.; Boyarskikh, Vyacheslav Nature, Vol. 551, Issue 7682 https://doi.org/10.1038/nature24641	journal	November 2017
Enzymatic hydroxylation of an unactivated methylene C–H bond guided by molecular dynamics simulations Narayan, Alison R. H.; Jiménez-Osés, Gonzalo; Liu, Peng Nature Chemistry, Vol. 7, Issue 8 https://doi.org/10.1038/nchem.2285	journal	June 2015
Evolving artificial metalloenzymes via random mutagenesis Yang, Hao; Swartz, Alan M.; Park, Hyun June Nature Chemistry, Vol. 10, Issue 3 https://doi.org/10.1038/nchem.2927	journal	January 2018
Methods for the directed evolution of proteins Packer, Michael S.; Liu, David R. Nature Reviews Genetics, Vol. 16, Issue 7 https://doi.org/10.1038/nrg3927	journal	June 2015
Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3 C–H functionalization Zhang, Ruijie K.; Chen, Kai; Huang, Xiongyi Nature, Vol. 565, Issue 7737 https://doi.org/10.1038/s41586-018-0808-5	journal	December 2018
Iridium( iii )-bis(imidazolinyl)phenyl catalysts for enantioselective C–H functionalization with ethyl diazoacetate Weldy, N. Mace; Schafer, A. G.; Owens, C. P. Chemical Science, Vol. 7, Issue 5 https://doi.org/10.1039/C6SC00190D	journal	January 2016
Selective functionalisation of saturated C–H bonds with metalloporphyrin catalysts Che, Chi-Ming; Lo, Vanessa Kar-Yan; Zhou, Cong-Ying Chemical Society Reviews, Vol. 40, Issue 4 https://doi.org/10.1039/c0cs00142b	journal	January 2011
Crystallization and preliminary X-ray diffraction analysis of a cytochrome P450 (CYP119) from Sulfolobus solfataricus Park, Sam-Yong; Yamane, Kazuhide; Adachi, Shin-ichi Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 9 https://doi.org/10.1107/S0907444900008234	journal	September 2000
Molecular Recognition in the Selective Oxygenation of Saturated C-H Bonds by a Dimanganese Catalyst Das, S. Science, Vol. 312, Issue 5782 https://doi.org/10.1126/science.1127899	journal	June 2006
An artificial metalloenzyme with the kinetics of native enzymes Dydio, P.; Key, H. M.; Nazarenko, A. Science, Vol. 354, Issue 6308 https://doi.org/10.1126/science.aah4427	journal	October 2016
Site-selective enzymatic C‒H amidation for synthesis of diverse lactams Cho, Inha; Jia, Zhi-Jun; Arnold, Frances H. Science, Vol. 364, Issue 6440 https://doi.org/10.1126/science.aaw9068	journal	May 2019
Artificial Metalloenzymes Based on the Biotin-Streptavidin Technology: Enzymatic Cascades and Directed Evolution Deliz, Liang, Alexandria; Joan, Serrano-Plana,; L., Peterson, Ryan American Chemical Society https://doi.org/10.5451/unibas-ep70592	text	January 2019

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