Combining chemistry and protein engineering for new-to-nature biocatalysis

Miller, David C.; Athavale, Soumitra V.; Arnold, Frances H.

doi:10.1038/s44160-021-00008-x

Combining chemistry and protein engineering for new-to-nature biocatalysis

Journal Article · Wed Jan 12 00:00:00 EST 2022 · Nature Synthesis

DOI:https://doi.org/10.1038/s44160-021-00008-x· OSTI ID:1854345

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California Institute of Technology (CalTech), Pasadena, CA (United States); California Institute of Technology
California Institute of Technology (CalTech), Pasadena, CA (United States)

Biocatalysis, the application of enzymes to solve synthetic problems of human import, has blossomed into a powerful technology for chemical innovation. In the past decade, a threefold partnership, where nature provides blueprints for enzymatic catalysis, chemists introduce innovative activity modes with abiological substrates, and protein engineers develop new tools and algorithms to tune and improve enzymatic function, has unveiled the frontier of new-to-nature enzyme catalysis. In this Perspective, we highlight examples of interdisciplinary studies, which have helped to expand the scope of biocatalysis, including concepts of enzymatic versatility explored through the lens of biomimicry, to achieve activities and selectivities beyond those currently possible with chemocatalysis. We indicate how modern tools, such as directed evolution, computational protein design and machine learning-based protein engineering methods, have already impacted and will continue to influence enzyme engineering for new abiological transformations. As a result, a sustained collaborative effort across disciplines is anticipated to spur further advances in biocatalysis in the coming years.

View Accepted Manuscript (DOE)

Research Organization:: California Institute of Technology (CalTech), Pasadena, CA (United States)

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

Grant/Contract Number:: SC0021141

OSTI ID:: 1854345

Journal Information:: Nature Synthesis, Journal Name: Nature Synthesis Journal Issue: 1 Vol. 1; ISSN 2731-0582

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

References (51)

Light-Driven Flavin-Based Biocatalysis Grosheva, Daria; Hyster*, Todd K. Flavin-Based Catalysis https://doi.org/10.1002/9783527830138.ch12	book	June 2021
Enantioselective Intramolecular CH Amination Catalyzed by Engineered Cytochrome P450 Enzymes In Vitro and In Vivo McIntosh, John A.; Coelho, Pedro S.; Farwell, Christopher C. Angewandte Chemie International Edition, Vol. 52, Issue 35 https://doi.org/10.1002/anie.201304401	journal	July 2013
Expanding the Enzyme Universe: Accessing Non-Natural Reactions by Mechanism-Guided Directed Evolution Renata, Hans; Wang, Z. Jane; Arnold, Frances H. Angewandte Chemie International Edition, Vol. 54, Issue 11 https://doi.org/10.1002/anie.201409470	journal	February 2015
Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin-Based Catalysts Bordeaux, Melanie; Tyagi, Vikas; Fasan, Rudi Angewandte Chemie International Edition, Vol. 54, Issue 6 https://doi.org/10.1002/anie.201409928	journal	December 2014
Innovation by Evolution: Bringing New Chemistry to Life (Nobel Lecture) Arnold, Frances H. Angewandte Chemie International Edition, Vol. 58, Issue 41 https://doi.org/10.1002/anie.201907729	journal	August 2019
Biocatalytic, Intermolecular C−H Bond Functionalization for the Synthesis of Enantioenriched Amides Athavale, Soumitra V.; Gao, Shilong; Liu, Zhen Angewandte Chemie International Edition, Vol. 60, Issue 47 https://doi.org/10.1002/anie.202110873	journal	October 2021
Beyond ferryl-mediated hydroxylation: 40 years of the rebound mechanism and C–H activation Huang, Xiongyi; Groves, John T. JBIC Journal of Biological Inorganic Chemistry, Vol. 22, Issue 2-3 https://doi.org/10.1007/s00775-016-1414-3	journal	December 2016
Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities Miller, David C.; Tarantino, Kyle T.; Knowles, Robert R. Topics in Current Chemistry, Vol. 374, Issue 3 https://doi.org/10.1007/s41061-016-0030-6	journal	May 2016
Directed evolution of enzyme catalysts Kuchner, Olga; Arnold, Frances H. Trends in Biotechnology, Vol. 15, Issue 12 https://doi.org/10.1016/S0167-7799(97)01138-4	journal	December 1997
Biocatalysis for the synthesis of pharmaceuticals and pharmaceutical intermediates Sun, Huihua; Zhang, Hongfang; Ang, Ee Lui Bioorganic & Medicinal Chemistry, Vol. 26, Issue 7 https://doi.org/10.1016/j.bmc.2017.06.043	journal	April 2018
Informed training set design enables efficient machine learning-assisted directed protein evolution Wittmann, Bruce J.; Yue, Yisong; Arnold, Frances H. Cell Systems https://doi.org/10.1016/j.cels.2021.07.008	journal	August 2021
A brief history of the contribution of metalloporphyrin models to cytochrome P450 chemistry and oxidation catalysis Mansuy, Daniel Comptes Rendus Chimie, Vol. 10, Issue 4-5 https://doi.org/10.1016/j.crci.2006.11.001	journal	April 2007
Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer Yang, Yang; Arnold, Frances H. Accounts of Chemical Research, Vol. 54, Issue 5 https://doi.org/10.1021/acs.accounts.0c00591	journal	January 2021
Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes Flanigan, Darrin M.; Romanov-Michailidis, Fedor; White, Nicholas A. Chemical Reviews, Vol. 115, Issue 17 https://doi.org/10.1021/acs.chemrev.5b00060	journal	May 2015
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
Power of Biocatalysis for Organic Synthesis Winkler, Christoph K.; Schrittwieser, Joerg H.; Kroutil, Wolfgang ACS Central Science, Vol. 7, Issue 1 https://doi.org/10.1021/acscentsci.0c01496	journal	January 2021
Diverse Engineered Heme Proteins Enable Stereodivergent Cyclopropanation of Unactivated Alkenes Knight, Anders M.; Kan, S. B. Jennifer; Lewis, Russell D. ACS Central Science, Vol. 4, Issue 3 https://doi.org/10.1021/acscentsci.7b00548	journal	February 2018
Computational Design of Enone-Binding Proteins with Catalytic Activity for the Morita–Baylis–Hillman Reaction Bjelic, Sinisa; Nivón, Lucas G.; Çelebi-Ölçüm, Nihan ACS Chemical Biology, Vol. 8, Issue 4 https://doi.org/10.1021/cb3006227	journal	January 2013
Biomimetic Reactions Catalyzed by Cyclodextrins and Their Derivatives Breslow, Ronald; Dong, Steven D. Chemical Reviews, Vol. 98, Issue 5 https://doi.org/10.1021/cr970011j	journal	July 1998
Functionalized nitrogen atom transfer catalyzed by cytochrome P-450 Svastits, Edmund W.; Dawson, John H.; Breslow, Ronald Journal of the American Chemical Society, Vol. 107, Issue 22 https://doi.org/10.1021/ja00308a064	journal	October 1985
Intramolecular nitrene carbon-hydrogen insertions mediated by transition-metal complexes as nitrogen analogs of cytochrome P-450 reactions Breslow, Ronald; Gellman, Samuel H. Journal of the American Chemical Society, Vol. 105, Issue 22 https://doi.org/10.1021/ja00360a039	journal	October 1983
Conversion of a Zinc Disilazide to a Zinc Hydride Mediated by LiCl Mukherjee, Debabrata; Ellern, Arkady; Sadow, Aaron D. Journal of the American Chemical Society, Vol. 132, Issue 22 https://doi.org/10.1021/ja102323g	journal	June 2010
Zinc Catalysts for On-Demand Hydrogen Generation and Carbon Dioxide Functionalization Sattler, Wesley; Parkin, Gerard Journal of the American Chemical Society, Vol. 134, Issue 42 https://doi.org/10.1021/ja308500s	journal	October 2012
Enzymatic Primary Amination of Benzylic and Allylic C(sp ³ )–H Bonds Jia, Zhi-Jun; Gao, Shilong; Arnold, Frances H. Journal of the American Chemical Society, Vol. 142, Issue 23 https://doi.org/10.1021/jacs.0c03428	journal	May 2020
Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins Page, Claire G.; Cooper, Simon J.; DeHovitz, Jacob S. Journal of the American Chemical Society, Vol. 143, Issue 1 https://doi.org/10.1021/jacs.0c11462	journal	December 2020
Ground-State Electron Transfer as an Initiation Mechanism for Biocatalytic C–C Bond Forming Reactions Fu, Haigen; Lam, Heather; Emmanuel, Megan A. Journal of the American Chemical Society, Vol. 143, Issue 25 https://doi.org/10.1021/jacs.1c04334	journal	June 2021
Photoenzymatic Synthesis of α-Tertiary Amines by Engineered Flavin-Dependent “Ene”-Reductases Gao, Xin; Turek-Herman, Joshua R.; Choi, Young Joo Journal of the American Chemical Society, Vol. 143, Issue 47 https://doi.org/10.1021/jacs.1c09828	journal	November 2021
Chemomimetic Biocatalysis: Exploiting the Synthetic Potential of Cofactor-Dependent Enzymes To Create New Catalysts Prier, Christopher K.; Arnold, Frances H. Journal of the American Chemical Society, Vol. 137, Issue 44 https://doi.org/10.1021/jacs.5b09348	journal	November 2015
Enantioselective Hydrogen Atom Transfer: Discovery of Catalytic Promiscuity in Flavin-Dependent ‘Ene’-Reductases Sandoval, Braddock A.; Meichan, Andrew J.; Hyster, Todd K. Journal of the American Chemical Society, Vol. 139, Issue 33 https://doi.org/10.1021/jacs.7b05468	journal	August 2017
Mechanism-Guided Design and Discovery of Efficient Cytochrome P450-Derived C–H Amination Biocatalysts Steck, Viktoria; Kolev, Joshua N.; Ren, Xinkun Journal of the American Chemical Society, Vol. 142, Issue 23 https://doi.org/10.1021/jacs.9b12859	journal	May 2020
Natural Selection and the Concept of a Protein Space Maynard Smith, John Nature, Vol. 225, Issue 5232 https://doi.org/10.1038/225563a0	journal	February 1970
Kemp elimination catalysts by computational enzyme design Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M. Nature, Vol. 453, Issue 7192, p. 190-195 https://doi.org/10.1038/nature06879	journal	March 2008
Precision is essential for efficient catalysis in an evolved Kemp eliminase Blomberg, Rebecca; Kries, Hajo; Pinkas, Daniel M. Nature, Vol. 503, Issue 7476 https://doi.org/10.1038/nature12623	journal	October 2013
The coming of age of de novo protein design Huang, Po-Ssu; Boyken, Scott E.; Baker, David Nature, Vol. 537, Issue 7620 https://doi.org/10.1038/nature19946	journal	September 2016
Accessing non-natural reactivity by irradiating nicotinamide-dependent enzymes with light Emmanuel, Megan A.; Greenberg, Norman R.; Oblinsky, Daniel G. Nature, Vol. 540, Issue 7633 https://doi.org/10.1038/nature20569	journal	December 2016
Flavin-dependent halogenases catalyze enantioselective olefin halocyclization Mondal, Dibyendu; Fisher, Brian F.; Jiang, Yuhua Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-23503-3	journal	June 2021
Abiotic reduction of ketones with silanes catalysed by carbonic anhydrase through an enzymatic zinc hydride Ji, Pengfei; Park, Jeeyoung; Gu, Yang Nature Chemistry, Vol. 13, Issue 4 https://doi.org/10.1038/s41557-020-00633-7	journal	February 2021
Photoenzymatic enantioselective intermolecular radical hydroalkylation Huang, Xiaoqiang; Wang, Binju; Wang, Yajie Nature, Vol. 584, Issue 7819 https://doi.org/10.1038/s41586-020-2406-6	journal	June 2020
Engineering new catalytic activities in enzymes Chen, Kai; Arnold, Frances H. Nature Catalysis, Vol. 3, Issue 3 https://doi.org/10.1038/s41929-019-0385-5	journal	January 2020
The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis Sheldon, Roger A.; Brady, Dean; Bode, Moira L. Chemical Science, Vol. 11, Issue 10 https://doi.org/10.1039/C9SC05746C	journal	January 2020
Tosylamidation of cyclohexane by a cytochrome P-450 model Breslow, Ronald; Gellman, Samuel H. Journal of the Chemical Society, Chemical Communications, Issue 24 https://doi.org/10.1039/c39820001400	journal	January 1982
Machine learning-assisted directed protein evolution with combinatorial libraries Wu, Zachary; Kan, S. B. Jennifer; Lewis, Russell D. Proceedings of the National Academy of Sciences, Vol. 116, Issue 18 https://doi.org/10.1073/pnas.1901979116	journal	April 2019
Biomimetic Chemistry: Biology as an Inspiration Breslow, Ronald Journal of Biological Chemistry, Vol. 284, Issue 3 https://doi.org/10.1074/jbc.X800011200	journal	September 2008
Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture Savile, C. K.; Janey, J. M.; Mundorff, E. C. Science, Vol. 329, Issue 5989 https://doi.org/10.1126/science.1188934	journal	June 2010
Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction Siegel, J. B.; Zanghellini, A.; Lovick, H. M. Science, Vol. 329, Issue 5989 https://doi.org/10.1126/science.1190239	journal	July 2010
Enzymatic construction of highly strained carbocycles Chen, Kai; Huang, Xiongyi; Kan, S. B. Jennifer Science, Vol. 360, Issue 6384 https://doi.org/10.1126/science.aar4239	journal	April 2018
Photoexcitation of flavoenzymes enables a stereoselective radical cyclization Biegasiewicz, Kyle F.; Cooper, Simon J.; Gao, Xin Science, Vol. 364, Issue 6446 https://doi.org/10.1126/science.aaw1143	journal	June 2019
Design of an in vitro biocatalytic cascade for the manufacture of islatravir Huffman, Mark A.; Fryszkowska, Anna; Alvizo, Oscar Science, Vol. 366, Issue 6470 https://doi.org/10.1126/science.aay8484	journal	December 2019
Cell-free chemoenzymatic starch synthesis from carbon dioxide Cai, Tao; Sun, Hongbing; Qiao, Jing Science, Vol. 373, Issue 6562 https://doi.org/10.1126/science.abh4049	journal	September 2021
Enzyme Promiscuity: A Mechanistic and Evolutionary Perspective Khersonsky, Olga; Tawfik, Dan S. Annual Review of Biochemistry, Vol. 79, Issue 1, p. 471-505 https://doi.org/10.1146/annurev-biochem-030409-143718	journal	June 2010
Directed Evolution of Protein Catalysts Zeymer, Cathleen; Hilvert, Donald Annual Review of Biochemistry, Vol. 87, Issue 1 https://doi.org/10.1146/annurev-biochem-062917-012034	journal	June 2018

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