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Title: Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis

Abstract

Living organisms rely on simultaneous reactions catalysed by mutually compatible and selective enzymes to synthesize complex natural products and other metabolites. To combine the advantages of these biological systems with the reactivity of artificial chemical catalysts, chemists have devised sequential, concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and artificial catalysts. Cooperative chemoenzymatic reactions consist of interconnected processes that generate products in yields and selectivities that cannot be obtained when the two reactions are carried out sequentially with their respective substrates. However, such reactions are difficult to develop because chemical and enzymatic catalysts generally operate in different media at different temperatures and can deactivate each other. Owing to these constraints, the vast majority of cooperative chemoenzymatic processes that have been reported over the past 30 years can be divided into just two categories: chemoenzymatic dynamic kinetic resolutions of racemic alcohols and amines, and enzymatic reactions requiring the simultaneous regeneration of a cofactor. New approaches to the development of chemoenzymatic reactions are needed to enable valuable chemical transformations beyond this scope. Here in this paper we report a class of cooperative chemoenzymatic reaction that combines photocatalysts that isomerize alkenes with ene-reductases that reduce carbon–carbon double bonds to generate valuable enantioenriched products.more » This method enables the stereoconvergent reduction of E/Zmixtures of alkenes or reduction of the unreactive stereoisomers of alkenes in yields and enantiomeric excesses that match those obtained from the reduction of the pure, more reactive isomers. The system affords a range of enantioenriched precursors to biologically active compounds. More generally, these results show that the compatibility between photocatalysts and enzymes enables chemoenzymatic processes beyond cofactor regeneration and provides a general strategy for converting stereoselective enzymatic reactions into stereoconvergent ones.« less

Authors:
 [1];  [2];  [3];  [1]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
  2. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemical and Biomolecular Engineering
  3. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemical and Biomolecular Engineering, and Dept. of Chemistry, and Dept. of Biochemistry, and Dept. of of Bioengineering, and Carl R. Woese Inst. for Genomic Biology
Publication Date:
Research Org.:
Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1470980
Grant/Contract Number:  
SC0018420
Resource Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 560; Journal Issue: 7718; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Litman, Zachary C., Wang, Yajie, Zhao, Huimin, and Hartwig, John F. Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis. United States: N. p., 2018. Web. doi:10.1038/s41586-018-0413-7.
Litman, Zachary C., Wang, Yajie, Zhao, Huimin, & Hartwig, John F. Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis. United States. doi:https://doi.org/10.1038/s41586-018-0413-7
Litman, Zachary C., Wang, Yajie, Zhao, Huimin, and Hartwig, John F. Thu . "Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis". United States. doi:https://doi.org/10.1038/s41586-018-0413-7. https://www.osti.gov/servlets/purl/1470980.
@article{osti_1470980,
title = {Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis},
author = {Litman, Zachary C. and Wang, Yajie and Zhao, Huimin and Hartwig, John F.},
abstractNote = {Living organisms rely on simultaneous reactions catalysed by mutually compatible and selective enzymes to synthesize complex natural products and other metabolites. To combine the advantages of these biological systems with the reactivity of artificial chemical catalysts, chemists have devised sequential, concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and artificial catalysts. Cooperative chemoenzymatic reactions consist of interconnected processes that generate products in yields and selectivities that cannot be obtained when the two reactions are carried out sequentially with their respective substrates. However, such reactions are difficult to develop because chemical and enzymatic catalysts generally operate in different media at different temperatures and can deactivate each other. Owing to these constraints, the vast majority of cooperative chemoenzymatic processes that have been reported over the past 30 years can be divided into just two categories: chemoenzymatic dynamic kinetic resolutions of racemic alcohols and amines, and enzymatic reactions requiring the simultaneous regeneration of a cofactor. New approaches to the development of chemoenzymatic reactions are needed to enable valuable chemical transformations beyond this scope. Here in this paper we report a class of cooperative chemoenzymatic reaction that combines photocatalysts that isomerize alkenes with ene-reductases that reduce carbon–carbon double bonds to generate valuable enantioenriched products. This method enables the stereoconvergent reduction of E/Zmixtures of alkenes or reduction of the unreactive stereoisomers of alkenes in yields and enantiomeric excesses that match those obtained from the reduction of the pure, more reactive isomers. The system affords a range of enantioenriched precursors to biologically active compounds. More generally, these results show that the compatibility between photocatalysts and enzymes enables chemoenzymatic processes beyond cofactor regeneration and provides a general strategy for converting stereoselective enzymatic reactions into stereoconvergent ones.},
doi = {10.1038/s41586-018-0413-7},
journal = {Nature (London)},
number = 7718,
volume = 560,
place = {United States},
year = {2018},
month = {8}
}

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Works referenced in this record:

Asymmetric Bioreduction of Alkenes Using Ene–Reductases YersER and KYE1 and Effects of Organic Solvents
journal, May 2011

  • Yanto, Yanto; Winkler, Christoph K.; Lohr, Stephanie
  • Organic Letters, Vol. 13, Issue 10
  • DOI: 10.1021/ol200394p

A Bio-Inspired, Catalytic EZ Isomerization of Activated Olefins
journal, August 2015

  • Metternich, Jan B.; Gilmour, Ryan
  • Journal of the American Chemical Society, Vol. 137, Issue 35
  • DOI: 10.1021/jacs.5b07136

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines
journal, March 2015

  • Verho, Oscar; Bäckvall, Jan-E.
  • Journal of the American Chemical Society, Vol. 137, Issue 12
  • DOI: 10.1021/jacs.5b01031

Enantioselective Aza-Ene-type Reactions of Enamides with Gold Carbenes Generated from α-Diazoesters
journal, February 2017

  • Zhao, Feng; Li, Nan; Zhang, Tao
  • Angewandte Chemie International Edition, Vol. 56, Issue 12
  • DOI: 10.1002/anie.201612208

Dynamic Kinetic Resolution of Racemic β-Haloalcohols: Direct Access to Enantioenriched Epoxides
journal, October 2008

  • Haak, Robert M.; Berthiol, Florian; Jerphagnon, Thomas
  • Journal of the American Chemical Society, Vol. 130, Issue 41
  • DOI: 10.1021/ja805128x

Multistep One-Pot Reactions Combining Biocatalysts and Chemical Catalysts for Asymmetric Synthesis
journal, November 2013

  • Denard, Carl A.; Hartwig, John F.; Zhao, Huimin
  • ACS Catalysis, Vol. 3, Issue 12
  • DOI: 10.1021/cs400633a

Old Yellow Enzyme-mediated reduction of β-cyano-α,β-unsaturated esters for the synthesis of chiral building blocks: stereochemical analysis of the reaction
journal, January 2013

  • Brenna, Elisabetta; Gatti, Francesco G.; Manfredi, Alessia
  • Catalysis Science & Technology, Vol. 3, Issue 4
  • DOI: 10.1039/c3cy20804d

Combining Rh-Catalyzed Diazocoupling and Enzymatic Reduction To Efficiently Synthesize Enantioenriched 2-Substituted Succinate Derivatives
journal, March 2017


Preparation of Chiral 3-Arylpyrrolidines via the Enantioselective 1,4-Addition of Arylboronic Acids to Fumaric Esters Catalyzed by Rh(I)/Chiral Diene Complexes
journal, May 2012

  • Chung, Yu-Chiang,; Janmanchi, Damodar; Wu, Hsyueh-Liang
  • Organic Letters, Vol. 14, Issue 11
  • DOI: 10.1021/ol300980k

Comparison of Three Enoate Reductases and their Potential Use for Biotransformations
journal, June 2007

  • Chaparro-Riggers, Javier F.; Rogers, Thomas A.; Vazquez-Figueroa, Eduardo
  • Advanced Synthesis & Catalysis, Vol. 349, Issue 8-9
  • DOI: 10.1002/adsc.200700074

Artificial concurrent catalytic processes involving enzymes
journal, January 2015

  • Köhler, Valentin; Turner, Nicholas J.
  • Chemical Communications, Vol. 51, Issue 3
  • DOI: 10.1039/C4CC07277D

Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes
journal, November 2012

  • Köhler, V.; Wilson, Y. M.; Dürrenberger, M.
  • Nature Chemistry, Vol. 5, Issue 2
  • DOI: 10.1038/nchem.1498

Photocatalytic EZ Isomerization of Polarized Alkenes Inspired by the Visual Cycle: Mechanistic Dichotomy and Origin of Selectivity
journal, July 2017

  • Metternich, Jan B.; Artiukhin, Denis G.; Holland, Mareike C.
  • The Journal of Organic Chemistry, Vol. 82, Issue 19
  • DOI: 10.1021/acs.joc.7b01281

Highly efficient asymmetric hydrogenation of cyano-substituted acrylate esters for synthesis of chiral γ-lactams and amino acids
journal, January 2016

  • Kong, Duanyang; Li, Meina; Wang, Rui
  • Organic & Biomolecular Chemistry, Vol. 14, Issue 4
  • DOI: 10.1039/C5OB02422F

Opportunities and challenges for combining chemo- and biocatalysis
journal, January 2018


Expanding the boundary of biocatalysis: design and optimization of in vitro tandem catalytic reactions for biochemical production
journal, February 2018

  • Wang, Yajie; Ren, Hengqian; Zhao, Huimin
  • Critical Reviews in Biochemistry and Molecular Biology, Vol. 53, Issue 2
  • DOI: 10.1080/10409238.2018.1431201

Stereocomplementary Bioreduction of α,β-Unsaturated Dicarboxylic Acids and Dimethyl Esters using Enoate Reductases:  Enzyme- and Substrate-Based Stereocontrol
journal, December 2007

  • Stueckler, Clemens; Hall, Mélanie; Ehammer, Heidemarie
  • Organic Letters, Vol. 9, Issue 26
  • DOI: 10.1021/ol7019185

Contra-Thermodynamic, Photocatalytic EZ Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two-Dimensional Chemical Space
journal, February 2018

  • Molloy, John J.; Metternich, Jan B.; Daniliuc, Constantin G.
  • Angewandte Chemie International Edition, Vol. 57, Issue 12
  • DOI: 10.1002/anie.201800286

Facile Synthesis of Z -Alkenes via Uphill Catalysis
journal, February 2014

  • Singh, Kamaljeet; Staig, Shannon J.; Weaver, Jimmie D.
  • Journal of the American Chemical Society, Vol. 136, Issue 14
  • DOI: 10.1021/ja5019749

Cooperative Tandem Catalysis by an Organometallic Complex and a Metalloenzyme
journal, November 2013

  • Denard, Carl A.; Huang, Hua; Bartlett, Mark J.
  • Angewandte Chemie International Edition, Vol. 53, Issue 2
  • DOI: 10.1002/anie.201305778

Photocatalytic E → Z Isomerization of Alkenes
journal, October 2016


Catalytic Asymmetric Hydrogenation of α-CF 3 - or β-CF 3 -Substituted Acrylic Acids using Rhodium(I) Complexes with a Combination of Chiral and Achiral Ligands
journal, November 2013

  • Dong, Kaiwu; Li, Yang; Wang, Zheng
  • Angewandte Chemie International Edition, Vol. 52, Issue 52
  • DOI: 10.1002/anie.201307903

Cooperative Tandem Catalysis by an Organometallic Complex and a Metalloenzyme
journal, November 2013

  • Denard, Carl A.; Huang, Hua; Bartlett, Mark J.
  • Angewandte Chemie, Vol. 126, Issue 2
  • DOI: 10.1002/ange.201305778

Contra-Thermodynamic, Photocatalytic EZ Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two-Dimensional Chemical Space
journal, February 2018

  • Molloy, John J.; Metternich, Jan B.; Daniliuc, Constantin G.
  • Angewandte Chemie, Vol. 130, Issue 12
  • DOI: 10.1002/ange.201800286

    Works referencing / citing this record:

    Concurrent Asymmetric Reactions Combining Photocatalysis and Enzyme Catalysis: Direct Enantioselective Synthesis of 2,2-Disubstituted Indol-3-ones from 2-Arylindoles
    journal, December 2018

    • Ding, Xuan; Dong, Chun-Lin; Guan, Zhi
    • Angewandte Chemie International Edition, Vol. 58, Issue 1
    • DOI: 10.1002/anie.201811085

    Organic semiconductor photocatalyst can bifunctionalize arenes and heteroarenes
    journal, July 2019

    • Ghosh, Indrajit; Khamrai, Jagadish; Savateev, Aleksandr
    • Science, Vol. 365, Issue 6451
    • DOI: 10.1126/science.aaw3254

    Copper‐Catalyzed Enantioselective Formation of C−CF 3 Centers from β‐CF 3 ‐Substituted Acrylates and Acrylonitriles
    journal, October 2019

    • Poutrel, Pauline; Ivanova, Maria V.; Pannecoucke, Xavier
    • Chemistry – A European Journal, Vol. 25, Issue 67
    • DOI: 10.1002/chem.201904192

    Concurrent Asymmetric Reactions Combining Photocatalysis and Enzyme Catalysis: Direct Enantioselective Synthesis of 2,2-Disubstituted Indol-3-ones from 2-Arylindoles
    journal, December 2018

    • Ding, Xuan; Dong, Chun-Lin; Guan, Zhi
    • Angewandte Chemie International Edition, Vol. 58, Issue 1
    • DOI: 10.1002/anie.201811085

    Copper‐Catalyzed Enantioselective Formation of C−CF 3 Centers from β‐CF 3 ‐Substituted Acrylates and Acrylonitriles
    journal, October 2019

    • Poutrel, Pauline; Ivanova, Maria V.; Pannecoucke, Xavier
    • Chemistry – A European Journal, Vol. 25, Issue 67
    • DOI: 10.1002/chem.201904192

    Organic semiconductor photocatalyst can bifunctionalize arenes and heteroarenes
    journal, July 2019

    • Ghosh, Indrajit; Khamrai, Jagadish; Savateev, Aleksandr
    • Science, Vol. 365, Issue 6451
    • DOI: 10.1126/science.aaw3254

    Photoenzymatic Approaches in Organic Synthesis
    journal, August 2019

    • Chen, Jie; Guan, Zhi; He, Yan‐Hong
    • Asian Journal of Organic Chemistry, Vol. 8, Issue 10
    • DOI: 10.1002/ajoc.201900427

    Photoenzymatic Catalysis Enables Radical‐Mediated Ketone Reduction in Ene‐Reductases
    journal, May 2019

    • Sandoval, Braddock A.; Kurtoic, Sarah I.; Chung, Megan M.
    • Angewandte Chemie, Vol. 131, Issue 26
    • DOI: 10.1002/ange.201902005

    Positionelle und geometrische Isomerisierung von Alkenen: der Gipfel der Atomökonomie
    journal, July 2019

    • Molloy, John J.; Morack, Tobias; Gilmour, Ryan
    • Angewandte Chemie, Vol. 131, Issue 39
    • DOI: 10.1002/ange.201906124

    Photoenzymatic Catalysis Enables Radical‐Mediated Ketone Reduction in Ene‐Reductases
    journal, June 2019

    • Sandoval, Braddock A.; Kurtoic, Sarah I.; Chung, Megan M.
    • Angewandte Chemie International Edition, Vol. 58, Issue 26
    • DOI: 10.1002/anie.201902005

    Light‐Driven Kinetic Resolution of α‐Functionalized Carboxylic Acids Enabled by an Engineered Fatty Acid Photodecarboxylase
    journal, June 2019

    • Xu, Jian; Hu, Yujing; Fan, Jiajie
    • Angewandte Chemie International Edition, Vol. 58, Issue 25
    • DOI: 10.1002/anie.201903165

    Positional and Geometrical Isomerisation of Alkenes: The Pinnacle of Atom Economy
    journal, September 2019

    • Molloy, John J.; Morack, Tobias; Gilmour, Ryan
    • Angewandte Chemie International Edition, Vol. 58, Issue 39
    • DOI: 10.1002/anie.201906124

    Combined Photoredox/Enzymatic C−H Benzylic Hydroxylations
    journal, November 2019

    • Betori, Rick C.; May, Catherine M.; Scheidt, Karl A.
    • Angewandte Chemie International Edition, Vol. 58, Issue 46
    • DOI: 10.1002/anie.201909426

    Geometric EZ Isomerisation of Alkenyl Silanes by Selective Energy Transfer Catalysis: Stereodivergent Synthesis of Triarylethylenes via a Formal anti ‐Metallometallation
    journal, October 2019

    • Faßbender, Svenja I.; Molloy, John J.; Mück‐Lichtenfeld, Christian
    • Angewandte Chemie International Edition, Vol. 58, Issue 51
    • DOI: 10.1002/anie.201910169

    Biocatalysis Fueled by Light: On the Versatile Combination of Photocatalysis and Enzymes
    journal, June 2019


    Rh Doping in Pd Nanocubes Optimizes the Adsorption of 3‐Nitrostyrene towards Selective Hydrogenation of Vinyl Group
    journal, May 2019


    A Sequential Umpolung /Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ‐Lactones
    journal, April 2020

    • Maskeri, Mark A.; Schrader, Malte L.; Scheidt, Karl A.
    • Chemistry – A European Journal, Vol. 26, Issue 26
    • DOI: 10.1002/chem.202000747

    Reductive Amination and Enantioselective Amine Synthesis by Photoredox Catalysis: Reductive Amination and Enantioselective Amine Synthesis by Photoredox Catalysis
    journal, August 2019

    • Guo, Xingwei; Okamoto, Yasunori; Schreier, Mirjam R.
    • European Journal of Organic Chemistry, Vol. 2020, Issue 10
    • DOI: 10.1002/ejoc.201900777

    Enzyme–Metal Hybrid Catalysts for Chemoenzymatic Reactions
    journal, August 2019


    Recent Advances in Photocatalysis over Metal–Organic Frameworks‐Based Materials
    journal, December 2019


    Chemo-enzymatic cascades to produce cycloalkenes from bio-based resources
    journal, November 2019


    Highly active enzyme–metal nanohybrids synthesized in protein–polymer conjugates
    journal, June 2019


    Mild dynamic kinetic resolution of amines by coupled visible-light photoredox and enzyme catalysis
    journal, January 2018

    • Yang, Qiong; Zhao, Fengqian; Zhang, Na
    • Chemical Communications, Vol. 54, Issue 100
    • DOI: 10.1039/c8cc07990k

    Design and engineering of whole-cell biocatalytic cascades for the valorization of fatty acids
    journal, January 2020

    • Song, Ji-Won; Seo, Joo-Hyun; Oh, Doek-Kun
    • Catalysis Science & Technology, Vol. 10, Issue 1
    • DOI: 10.1039/c9cy01802f

    Enantiocomplementary decarboxylative hydroxylation combining photocatalysis and whole-cell biocatalysis in a one-pot cascade process
    journal, January 2019

    • Xu, Jian; Arkin, Mamatjan; Peng, Yongzhen
    • Green Chemistry, Vol. 21, Issue 8
    • DOI: 10.1039/c9gc00098d

    Advances in asymmetric visible-light photocatalysis, 2015–2019
    journal, January 2019

    • Jiang, Chunhui; Chen, Wei; Zheng, Wen-Hua
    • Organic & Biomolecular Chemistry, Vol. 17, Issue 38
    • DOI: 10.1039/c9ob01609k

    Revealing the transient conformations of a single flavin adenine dinucleotide using an aerolysin nanopore
    journal, January 2019

    • Li, Meng-Yin; Wang, Ya-Qian; Ying, Yi-Lun
    • Chemical Science, Vol. 10, Issue 44
    • DOI: 10.1039/c9sc03163d

    Selectivity through discriminatory induced fit enables switching of NAD (P)H coenzyme specificity in Old Yellow Enzyme ene‐reductases
    journal, May 2019

    • Iorgu, Andreea I.; Hedison, Tobias M.; Hay, Sam
    • The FEBS Journal, Vol. 286, Issue 16
    • DOI: 10.1111/febs.14862

    Nitromethane as a nitrogen donor in Schmidt-type formation of amides and nitriles
    journal, December 2019


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    journal, January 2020