Engineering a photoenzyme to use red light

Carceller, Jose M.; Jayee, Bhumika; Page, Claire G.; Oblinsky, Daniel G.; Mondragón-Solórzano, Gustavo; Chintala, Nithin; Cao, Jingzhe; Alassad, Zayed; Zhang, Zheyu; White, Nathaniel; Diaz, Danny J.; Ellington, Andrew D.; Scholes, Gregory D.; Dong, Sijia S.; Hyster, Todd K.

doi:10.1016/j.chempr.2024.09.017

Engineering a photoenzyme to use red light

Journal Article · Wed Oct 16 00:00:00 EDT 2024 · Chem

DOI:https://doi.org/10.1016/j.chempr.2024.09.017· OSTI ID:2477666

Carceller, Jose M. ^[1]; Jayee, Bhumika ^[2]; Page, Claire G. ^[3]; Oblinsky, Daniel G. ^[4]; Mondragón-Solórzano, Gustavo ^[2]; Chintala, Nithin ^[2]; Cao, Jingzhe ^[3]; Alassad, Zayed ^[4]; Zhang, Zheyu ^[2]; White, Nathaniel ^[2]; Diaz, Danny J. ^[5]; Ellington, Andrew D. ^[5]; Scholes, Gregory D. ^[4]; ^[2]; Hyster, Todd K. ^[3]

Princeton University, NJ (United States); Cornell University, Ithaca, NY (United States); Universitat Politècnica de València (Spain); Princeton University
Northeastern University, Boston, MA (United States)
Princeton University, NJ (United States); Cornell University, Ithaca, NY (United States)
Princeton University, NJ (United States)
University of Texas at Austin, TX (United States)

Photoenzymatic reactions involving flavin-dependent “ene”-reductases (EREDs) rely on protein-templated charge transfer (CT) complexes between the cofactor and substrate for radical initiation. These complexes typically absorb in the blue region of the electromagnetic spectrum. Here, we engineered an ERED to form CT complexes that absorb red light. Mechanistic studies indicate that red-light activity is due to the growth of a red-absorbing shoulder off the previously identified cyan absorption feature. Molecular dynamics simulations, docking, and excited-state calculations suggest that the cyan feature involves a π→π* transition on flavin, whereas the red-light absorption is a π→π* transition between flavin and the substrate. Furthermore, differences in the electronic transition are due to changes in the substrate-binding conformation and allosteric tuning of the electronic structure of the cofactor-substrate complex. Microenvironment tuning of the CT complex for red-light activity is observed with other engineered photoenzymatic reactions, highlighting this effect’s generality.

View Accepted Manuscript (DOE)

Research Organization:: Princeton University, NJ (United States)

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

Grant/Contract Number:: SC0019370

OSTI ID:: 2477666

Journal Information:: Chem, Journal Name: Chem Journal Issue: 2 Vol. 11; ISSN 2451-9294

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

References (38)

Synthesis of β‐Quaternary Lactams Using Photoenzymatic Catalysis Turek‐Herman, Joshua R.; Rosenberger, Mike; Hyster, Todd K. Asian Journal of Organic Chemistry, Vol. 12, Issue 8 https://doi.org/10.1002/ajoc.202300274	journal	July 2023
Engineering a Non‐Natural Photoenzyme for Improved Photon Efficiency** Nicholls, Bryce T.; Oblinsky, Daniel G.; Kurtoic, Sarah I. Angewandte Chemie International Edition, Vol. 61, Issue 2 https://doi.org/10.1002/anie.202113842	journal	December 2021
Covalent adducts of lactate oxidase. Photochemical formation and structure identification. Ghisla, S.; Massey, V.; Choong, Y. S. Journal of Biological Chemistry, Vol. 254, Issue 21 https://doi.org/10.1016/S0021-9258(19)86571-7	journal	November 1979
GFP Family: Structural Insights into Spectral Tuning Pakhomov, Alexey A.; Martynov, Vladimir I. Chemistry & Biology, Vol. 15, Issue 8 https://doi.org/10.1016/j.chembiol.2008.07.009	journal	August 2008
Fine spectral tuning of a flavin-binding fluorescent protein for multicolor imaging Nikolaev, Andrey; Yudenko, Anna; Smolentseva, Anastasia Journal of Biological Chemistry, Vol. 299, Issue 3 https://doi.org/10.1016/j.jbc.2023.102977	journal	March 2023
Directed Evolution of Gloeobacter violaceus Rhodopsin Spectral Properties Engqvist, Martin K. M.; McIsaac, R. Scott; Dollinger, Peter Journal of Molecular Biology, Vol. 427, Issue 1 https://doi.org/10.1016/j.jmb.2014.06.015	journal	January 2015
Multiconfiguration Pair-Density Functional Theory: A New Way To Treat Strongly Correlated Systems Gagliardi, Laura; Truhlar, Donald G.; Li Manni, Giovanni Accounts of Chemical Research, Vol. 50, Issue 1 https://doi.org/10.1021/acs.accounts.6b00471	journal	December 2016
Organic Photoredox Catalysis Romero, Nathan A.; Nicewicz, David A. Chemical Reviews, Vol. 116, Issue 17 https://doi.org/10.1021/acs.chemrev.6b00057	journal	June 2016
Photoredox Catalysis in Organic Chemistry Shaw, Megan H.; Twilton, Jack; MacMillan, David W. C. The Journal of Organic Chemistry, Vol. 81, Issue 16 https://doi.org/10.1021/acs.joc.6b01449	journal	June 2016
Radical Termination via β-Scission Enables Photoenzymatic Allylic Alkylation Using “Ene”-Reductases Laguerre, Netgie; Riehl, Paul S.; Oblinsky, Daniel G. ACS Catalysis, Vol. 12, Issue 15 https://doi.org/10.1021/acscatal.2c02294	journal	July 2022
Organic Synthesis Enabled by Light-Irradiation of EDA Complexes: Theoretical Background and Synthetic Applications Lima, Carolina G. S.; de M. Lima, Thiago; Duarte, Marcelo ACS Catalysis, Vol. 6, Issue 3 https://doi.org/10.1021/acscatal.5b02386	journal	January 2016
Development of a Platform for Near-Infrared Photoredox Catalysis Ravetz, Benjamin D.; Tay, Nicholas E. S.; Joe, Candice L. ACS Central Science, Vol. 6, Issue 11 https://doi.org/10.1021/acscentsci.0c00948	journal	October 2020
Discovery of Novel Gain-of-Function Mutations Guided by Structure-Based Deep Learning Shroff, Raghav; Cole, Austin W.; Diaz, Daniel J. ACS Synthetic Biology, Vol. 9, Issue 11 https://doi.org/10.1021/acssynbio.0c00345	journal	October 2020
Fresh Look at Electron-Transfer Mechanisms via the Donor/Acceptor Bindings in the Critical Encounter Complex Rosokha, Sergiy V.; Kochi, Jay K. Accounts of Chemical Research, Vol. 41, Issue 5 https://doi.org/10.1021/ar700256a	journal	May 2008
Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis Prier, Christopher K.; Rankic, Danica A.; MacMillan, David W. C. Chemical Reviews, Vol. 113, Issue 7 https://doi.org/10.1021/cr300503r	journal	March 2013
Multiconfiguration Pair-Density Functional Theory Li Manni, Giovanni; Carlson, Rebecca K.; Luo, Sijie Journal of Chemical Theory and Computation, Vol. 10, Issue 9 https://doi.org/10.1021/ct500483t	journal	August 2014
Second-order perturbation theory with a CASSCF reference function Andersson, Kerstin.; Malmqvist, Per Aake.; Roos, Bjoern O. The Journal of Physical Chemistry, Vol. 94, Issue 14 https://doi.org/10.1021/j100377a012	journal	July 1990
Structures of Complexes Formed by Halogen Molecules with Aromatic and with Oxygenated Solvents ¹ Mulliken, Robert S. Journal of the American Chemical Society, Vol. 72, Issue 1 https://doi.org/10.1021/ja01157a151	journal	January 1950
Synthetic Methods Driven by the Photoactivity of Electron Donor–Acceptor Complexes Crisenza, Giacomo E. M.; Mazzarella, Daniele; Melchiorre, Paolo Journal of the American Chemical Society, Vol. 142, Issue 12 https://doi.org/10.1021/jacs.0c01416	journal	March 2020
Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization Clayman, Phillip D.; Hyster, Todd K. Journal of the American Chemical Society, Vol. 142, Issue 37 https://doi.org/10.1021/jacs.0c07918	journal	August 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
Photoredox Catalysis Mediated by Tungsten(0) Arylisocyanides Fajardo, Javier; Barth, Alexandra T.; Morales, Maryann Journal of the American Chemical Society, Vol. 143, Issue 46 https://doi.org/10.1021/jacs.1c07617	journal	November 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
Overcoming Photochemical Limitations in Metallaphotoredox Catalysis: Red-Light-Driven C–N Cross-Coupling Goldschmid, Samantha L.; Soon Tay, Nicholas Eng; Joe, Candice L. Journal of the American Chemical Society, Vol. 144, Issue 49 https://doi.org/10.1021/jacs.2c09745	journal	November 2022
Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase Li, Xiankun; Page, Claire G.; Zanetti-Polzi, Laura Journal of the American Chemical Society, Vol. 145, Issue 24 https://doi.org/10.1021/jacs.3c02446	journal	June 2023
Regioselective Radical Alkylation of Arenes Using Evolved Photoenzymes Page, Claire G.; Cao, Jingzhe; Oblinsky, Daniel G. Journal of the American Chemical Society, Vol. 145, Issue 21 https://doi.org/10.1021/jacs.3c03607	journal	May 2023
Asymmetric Synthesis of α-Chloroamides via Photoenzymatic Hydroalkylation of Olefins Liu, Yi; Bender, Sophie G.; Sorigue, Damien Journal of the American Chemical Society, Vol. 146, Issue 11 https://doi.org/10.1021/jacs.4c00927	journal	March 2024
Red Light-Based Dual Photoredox Strategy Resembling the Z-Scheme of Natural Photosynthesis Glaser, Felix; Wenger, Oliver S. JACS Au, Vol. 2, Issue 6 https://doi.org/10.1021/jacsau.2c00265	journal	June 2022
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
Biosensor and machine learning-aided engineering of an amaryllidaceae enzyme d’Oelsnitz, Simon; Diaz, Daniel J.; Kim, Wantae Nature Communications, Vol. 15, Issue 1 https://doi.org/10.1038/s41467-024-46356-y	journal	March 2024
Photoredox catalysis using infrared light via triplet fusion upconversion Ravetz, Benjamin D.; Pun, Andrew B.; Churchill, Emily M. Nature, Vol. 565, Issue 7739 https://doi.org/10.1038/s41586-018-0835-2	journal	January 2019
Machine learning-aided engineering of hydrolases for PET depolymerization Lu, Hongyuan; Diaz, Daniel J.; Czarnecki, Natalie J. Nature, Vol. 604, Issue 7907 https://doi.org/10.1038/s41586-022-04599-z	journal	April 2022
An asymmetric sp3–sp3 cross-electrophile coupling using ‘ene’-reductases Fu, Haigen; Cao, Jingzhe; Qiao, Tianzhang Nature, Vol. 610, Issue 7931 https://doi.org/10.1038/s41586-022-05167-1	journal	August 2022
Squaraines as near-infrared photocatalysts for organic reactions Sellet, Nicolas; Sebbat, Malik; Elhabiri, Mourad Chemical Communications, Vol. 58, Issue 99 https://doi.org/10.1039/D2CC04707A	journal	January 2022
Applications of red light photoredox catalysis in organic synthesis Schade, Alexander H.; Mei, Liangyong Organic & Biomolecular Chemistry, Vol. 21, Issue 12 https://doi.org/10.1039/D3OB00107E	journal	January 2023
Tuning the Electrochemical and Photophysical Properties of Osmium-Based Photoredox Catalysts Bednářová, Eva; Beck, Logan R.; Rovis, Tomislav Synlett, Vol. 33, Issue 03 https://doi.org/10.1055/s-0041-1737792	journal	January 2022
Light‐Induced Alkylation and Dealkylation of the Flavin Nucleus Walker, Wolfram. H.; Hemmerich, Peter; Massey, Vincent European Journal of Biochemistry, Vol. 13, Issue 2 https://doi.org/10.1111/j.1432-1033.1970.tb00926.x	journal	April 1970
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

Similar Records

Engineering a Non‐Natural Photoenzyme for Improved Photon Efficiency**

Journal Article · Wed Dec 01 19:00:00 EST 2021 · Angewandte Chemie · OSTI ID:1833904

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
biocatalysis
density functional theory
photochemistry
photoenzyme
protein engineering
red light
ultrafast spectroscopy

Engineering a photoenzyme to use red light

Citation Formats

References (38)

Similar Records

Related Subjects