Embracing Nature’s Catalysts: A Viewpoint on the Future of Biocatalysis

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(15), P. 8418 - 8427

Published: June 4, 2020

ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTEmbracing Nature's Catalysts: A Viewpoint on the Future of BiocatalysisBernhard Hauer*Bernhard HauerInstitute Biochemistry and Technical Biochemistry, Department Universitaet Stuttgart, Allmandring 31, 70569 Germany*Email: [email protected]More by Bernhard Hauerhttp://orcid.org/0000-0001-6259-3348Cite this: ACS Catal. 2020, 10, 15, 8418–8427Publication Date (Web):June 4, 2020Publication History Received16 April 2020Published online4 June inissue 7 August 2020https://pubs.acs.org/doi/10.1021/acscatal.0c01708https://doi.org/10.1021/acscatal.0c01708article-commentaryACS PublicationsCopyright © 2020 American Chemical Society. This publication is available under these Terms Use. Request reuse permissions free to access through this site. Learn MoreArticle Views15099Altmetric-Citations190LEARN ABOUT THESE METRICSArticle Views are COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score a quantitative measure attention that research has received online. Clicking donut icon will load page at altmetric.com with additional details score social media presence for given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (1 MB) Get e-AlertscloseSUBJECTS:Biocatalysis,Catalysts,Chemical reactions,Industrial manufacturing,Peptides proteins e-Alerts

Language: Английский

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The road to fully programmable protein catalysis

Nature, Journal Year: 2022, Volume and Issue: 606(7912), P. 49 - 58

Published: June 1, 2022

Language: Английский

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Advances in ultrahigh-throughput screening for directed enzyme evolution

Chemical Society Reviews, Journal Year: 2019, Volume and Issue: 49(1), P. 233 - 262

Published: Dec. 9, 2019

This review summarizes how ultrahigh-throughput screening methods employ cells and biomimetic compartments to access the vast, unexplored diversity of biocatalysts with novel functions derived from directed evolution metagenomics libraries.

Language: Английский

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Stereodivergent Protein Engineering of a Lipase To Access All Possible Stereoisomers of Chiral Esters with Two Stereocenters

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(19), P. 7934 - 7945

Published: April 26, 2019

Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two thus four stereoisomeric products involved, obtaining enzyme mutants for individually accessing would be ideal. Although significant success has been achieved directed evolution of general, engineering one into highly stereocomplementary variants the full complement remains a challenge. Using Candida antarctica lipase B (CALB) as model, we report protein this needed transesterification reactions between racemic acids alcohols organic solvents. By generating screening less than 25 each isomer, >90% selectivity model reaction. This difficult feat was accomplished by developing strategy dubbed "focused rational iterative site-specific mutagenesis" (FRISM) at sites lining enzyme's binding pocket. The accumulation single mutations mutagenesis using restricted set rationally chosen amino allows formation ultrasmall mutant libraries requiring minimal stereoselectivity. crystal structure CALB variants, flanked MD simulations, uncovered source selectivity.

Language: Английский

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Enzymes revolutionize the bioproduction of value-added compounds: From enzyme discovery to special applications

Biotechnology Advances, Journal Year: 2020, Volume and Issue: 40, P. 107520 - 107520

Published: Jan. 23, 2020

Competitive sustainable production in industry demands new and better biocatalysts, optimized bioprocesses cost-effective product recovery. Our review sheds light on the progress made for individual steps towards these goals, starting with discovery of enzymes their corresponding genes. The are subsequently engineered to improve performance, combined reaction cascades expand scope integrated whole cells provide an optimal environment bioconversion. Strain engineering using synthetic biology methods tunes host production, design optimizes conditions downstream processing ensures efficient recovery commercially viable products. Selected examples illustrate how modified can revolutionize future-oriented applications ranging from bioproduction bulk-, specialty- fine chemicals, active pharmaceutical ingredients carbohydrates, over conversion greenhouse-gas CO2 into valuable products biocontrol agriculture, recycling polymers precious metals.

Language: Английский

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Protein Design: From the Aspect of Water Solubility and Stability

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(18), P. 14085 - 14179

Published: Aug. 3, 2022

Water solubility and structural stability are key merits for proteins defined by the primary sequence 3D-conformation. Their manipulation represents important aspects of protein design field that relies on accurate placement amino acids molecular interactions, guided underlying physiochemical principles. Emulated designer with well-defined properties both fuel knowledge-base more precise computational models used in various biomedical nanotechnological applications. The continuous developments science, increasing computing power, new algorithms, characterization techniques provide sophisticated toolkits beyond guess work. In this review, we summarize recent advances respect to water stability. After introducing fundamental rules, discuss transmembrane solubilization de novo design. Traditional strategies enhance introduced. designs stable complexes high-order assemblies covered. Computational methodologies behind these endeavors, including structure prediction programs, machine learning specialty software dedicated evaluation aggregation, discussed. findings opportunities Cryo-EM presented. This review provides an overview significant progress prospects

Language: Английский

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LmrR: A Privileged Scaffold for Artificial Metalloenzymes

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 52(3), P. 545 - 556

Published: Feb. 22, 2019

ConspectusThe biotechnological revolution has made it possible to create enzymes for many reactions by directed evolution. However, because of the immense number possibilities, availability that possess a basal level desired catalytic activity is prerequisite success. For new-to-nature reactions, artificial metalloenzymes (ARMs), which are rationally designed hybrids proteins and catalytically active transition-metal complexes, can be such starting point.This Account details our efforts toward creation ARMs catalysis reactions. Key approach notion binding substrates, is, effective molarity, key component achieving large accelerations in catalysis. this reason, designs based on multidrug resistance regulator LmrR, dimeric transcription factor with large, hydrophobic pocket at its dimer interface. In pocket, there two tryptophan moieties, important promiscuous planar conjugated compounds π-stacking. The machinery introduced either covalent linkage metal complex or via ligand supramolecular assembly, taking advantage central moieties noncovalent complexes.Designs chemical modification LmrR were successful catalysis, but proved too laborious practical. Therefore, expanded genetic code methodologies used introduce unnatural amino acids during biosynthesis vivo. These have been successfully applied Cu(II) catalyzed Friedel–Crafts alkylation indoles. extension MDRs from TetR family resulted capable providing opposite enantiomer product. We employed computationally assisted redesign these more selective hydratase, introducing glutamate as general base judicious position so activate direct incoming water nucleophile.A supramolecularly assembled ARM copper(II)–phenanthroline was giving rise up 94% ee. Also, hemin bound, resulting an heme enzyme enantioselective cyclopropanation importance structural dynamics suggested computational studies, showed pore open allow access substrates iron center, which, according crystal structure, deeply buried inside protein.Finally, assembly approaches combined both regulatory domain, specifically activated presence Fe(II) salts not Zn(II) salts.Our work demonstrates privileged scaffold design: It allows multiple methods even combinations these, variety different shows significant contribute activity. Moreover, well make LmrR-based highly suitable ultimate goal integration biosynthetic pathways vivo hybrid metabolism.

Language: Английский

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

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(1), P. 18 - 23

Published: Jan. 12, 2022

Language: Английский

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Droplet-based microfluidics

Nature Reviews Methods Primers, Journal Year: 2023, Volume and Issue: 3(1)

Published: April 20, 2023

Language: Английский

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A Brief History of De Novo Protein Design: Minimal, Rational, and Computational

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 433(20), P. 167160 - 167160

Published: July 21, 2021

Language: Английский

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