Hartwig, John F

Ward, Thomas R

eScholarship - University of California

UC BerkeleyUC Berkeley Previously Published WorksTitleNew “Cats” in the House: Chemistry Meets Biology in Artificial Metalloenzymes and Repurposed MetalloenzymesPermalinkhttps://escholarship.org/uc/item/23w5h3nfJournalAccounts of Chemical Research, 52(5)ISSN0001-4842AuthorsHartwig, John FWard, Thomas RPublication Date2019-05-21DOI10.1021/acs.accounts.9b00154 Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaNew “Cats” in the House: Chemistry Meets Biology in ArtificialMetalloenzymes and Repurposed MetalloenzymesGuest Editorial for the Accounts of Chemical Research special issue on “Artificial Metalloenzymes andAbiological Catalysis of Metalloenzymes”It is generally recognized that Wilson’s and Whitesides’ 1978paper entitled “Conversion of a Protein to a HomogeneousAsymmetric Hydrogenation Catalyst by Site-Specific Mod-ification with a Diphosphinerhodium(I) Moiety”1 marked thebirth of artificial metalloenzymes (ArMs). Such hybrid catalystsresult from combining a non-natural cofactor with a proteinscaffold. Thanks to the progress achieved in recombinantprotein engineering, ArMs have witnessed a revival in the past20 years. Accordingly, the challenges leading Wilson andWhitesides to conclude “The catalyst system...is not a practicalasymmetric catalyst” are being overcome. This issue ofAccounts of Chemical Research summarizes the progressachieved in the development of abiotic reactivity of naturalmetalloenzymes (repurposed enzymes, RepEns hereafter) andthe construction of ArMs for an even broader range of abioticprocesses.Despite the significant improvements achieved uponsubjecting an enzyme to multiple rounds of mutagenesis, therange of reactions catalyzed by enzymes is more limited thanthe range of reactions catalyzed by organometallic complexesor coordination complexes. To circumvent this restriction, andfascinated by the power of protein engineering and directedevolution, chemist’s (re)considered the possibility of introduc-ing abiotic cofactors within a protein around the turn of themillennium. Since then, the progress achieved in this field hasled to a wide range of new-to-nature reactions catalyzed byRepEns and ArMs, suggesting that essentially any water-compatible organometallic catalyst may be endowed with agenetically encoded and evolvable protein scaffold. Reactionscontained within this issue include Fischer−Tropsch reactions,cyclopropanations, C−H activation reactions, cross-couplings,olefin metatheses, (photo)catalytic CO2 reduction, site-selective post-translational protein modifications, and gatedmultielectron transfers.Capitalizing on a well-defined second coordination sphereprovided by the protein around the metal cofactor, researchershave modified (artificial) metalloenzymes to react withexquisite levels of selectivity including enantio-, diastereo-,chemo-, and regioselectivity. Such catalyst control has beenmade possible by combining the tools of chemistry andbiology. Half a century of organometallic catalysis offers a richground to select transition metal complexes that may bestowthe host protein with initial (abiotic) catalytic activity. Thisactivity then can be improved by genetic means. Identificationof critical amino-acid residues to subject to mutagenesis maybe guided by either computational information, an educatedguess, or random mutagenesis throughout the entire protein.Noteworthy improvements summarized in this issue includerates, turnover numbers, redox potentials, and biocompati-bility.Thanks to nearly 20 years of experience, privileged proteinscaffolds and robust anchoring strategies have been identifiedand made suitable for a broad range of catalytic applications.For example, hemoproteins bearing a non-native metal,cofactor, or decoy molecule have attracted significant interest,affording some of the best-in-class ArMs, with rates andturnover numbers rivaling natural enzymes. Cytochrome cb562has been used to design novel protein interfaces and assembliesand has been shown to act as an in vivo artificial hydrolase.Building on Whitesides’ lead, (strept)avidin has been shown toanchor nearly any biotinylated metal cofactor. Non-naturalamino acids have been used to introduce a photosensitizer orto anchor abiotic cofactors within the multidrug resistanceregulator LmR or the polyprolyl oligopeptidase POP. Finally,de novo artificial metalloenzyme design has led to three-stranded coiled-coils and four-helix bundles.We hope that this set of Accounts describing these types ofsystems highlights the rapid progress and long-term potentialof performing chemical synthesis with catalysts that combineconcepts and structures of homogeneous catalysis with thoseof biocatalysis.John F. Hartwig, Guest EditorUniversity of California, BerkeleyThomas R. Ward, Guest EditorUniversity of Basel■ AUTHOR INFORMATIONORCIDJohn F. Hartwig: 0000-0002-4157-468XThomas R. Ward: 0000-0001-8602-5468NotesViews expressed in this editorial are those of the authors andnot necessarily the views of the ACS.■ REFERENCES(1) Wilson, M. E.; Whitesides, G. M. Conversion of a Protein to aHomogeneous Asymmetric Hydrogenation Catalyst by Site-SpecificModification with a Diphosphinerhodium(I) Moiety. J. Am. Chem.Soc. 1978, 100, 306−307.Published: May 21, 2019Editorialpubs.acs.org/accountsCite This: Acc. Chem. Res. 2019, 52, 1145−1145© 2019 American Chemical Society 1145 DOI: 10.1021/acs.accounts.9b00154Acc. Chem. Res. 2019, 52, 1145−1145Downloaded via UNIV OF CALIFORNIA BERKELEY on July 10, 2019 at 00:00:54 (UTC).See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

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New “Cats” in the House: Chemistry Meets Biology in Artificial Metalloenzymes and Repurposed Metalloenzymes

Hartwig, John F.

Ward, Thomas R.

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New "Cats" in the House: Chemistry Meets Biology in Artificial Metalloenzymes and Repurposed Metalloenzymes

https://escholarship.org/content/qt23w5h3nf/qt23w5h3nf.pdf?t=q0nq8v

New "Cats" in the House: Chemistry Meets Biology in Artificial Metalloenzymes and Repurposed Metalloenzymes.

New "Cats" in the House: Chemistry Meets Biology in Artificial Metalloenzymes and Repurposed Metalloenzymes.

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