Startseite Lebenswissenschaften Artificial metalloenzymes in a nutshell: the quartet for efficient catalysis
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Artificial metalloenzymes in a nutshell: the quartet for efficient catalysis

  • Paul Ebensperger EMAIL logo und Claudia Jessen-Trefzer ORCID logo EMAIL logo
Veröffentlicht/Copyright: 18. Oktober 2021
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 403 Heft 4

Abstract

Artificial metalloenzymes combine the inherent reactivity of transition metal catalysis with the sophisticated reaction control of natural enzymes. By providing new opportunities in bioorthogonal chemistry and biocatalysis, artificial metalloenzymes have the potential to overcome certain limitations in both drug discovery and green chemistry or related research fields. Ongoing advances in organometallic catalysis, directed evolution, and bioinformatics are enabling the design of increasingly powerful systems that outperform conventional catalysis in a growing number of cases. Therefore, this review article collects challenges and opportunities in designing artificial metalloenzymes described in recent review articles. This will provide an equitable insight for those new to and interested in the field.

Keywords: biocatalysis; in vivo catalysis; new-to-nature reactivity; protein engineering
Corresponding authors: Paul Ebensperger and Claudia Jessen-Trefzer, Institute of Organic Chemistry, University of Freiburg, Albertstrasse 21, D-79104 Freiburg i. Br., Germany, E-mail: , (C. Jessen-Trefzer)

Funding source: Evangelisches Studienwerk Villigst

Award Identifier / Grant number: 851250

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The author thanks “Evangelisches Studienwerk Villigst” (851250) for financial support.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

Akabori, S., Izumi, Y., Fujii, Y., and Sakurai, S. (1956). An asymmetric catalyst. Nippon Kagaku Zassi 77: 1374–1378, https://doi.org/10.1246/nikkashi1948.77.1374.Suche in Google Scholar

Alizadeh, N. and Salimi, A. (2021). Multienzymes activity of metals and metal oxide nanomaterials: applications from biotechnology to medicine and environmental engineering. J. Nanobiotechnol. 19: 1–31, https://doi.org/10.1186/s12951-021-00771-1.Suche in Google Scholar PubMed PubMed Central

Basler, S., Studer, S., Zou, Y., Mori, T., Ota, Y., Camus, A., Bunzel, H.A., Helgeson, R.C., Houk, K.N., Jiménez-Osés, G., et al.. (2021). Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold. Nat. Chem. 13: 231–235, https://doi.org/10.1038/s41557-020-00628-4.Suche in Google Scholar PubMed

Biggs, G.S., Klein, O.J., Boss, S.R., and Barker, P.D. (2020). Unlocking the full evolutionary potential of artificial metalloenzymes through direct metal-protein coordination: a review of recent advances for catalyst development. Johnson Matthey Technol. Rev. 64: 407–418, https://doi.org/10.1595/205651320x15928204097766.Suche in Google Scholar

Churchfield, L.A. and Tezcan, F.A. (2019). Design and construction of functional supramolecular metalloprotein assemblies. Acc. Chem. Res. 52: 345–355, https://doi.org/10.1021/acs.accounts.8b00617.Suche in Google Scholar PubMed

Davis, H.J. and Ward, T.R. (2019). Artificial metalloenzymes: challenges and opportunities. ACS Cent. Sci. 5: 1120–1136, https://doi.org/10.1021/acscentsci.9b00397.Suche in Google Scholar PubMed PubMed Central

Destito, P., Vidal, C., López, F., and Mascareñas, J.L. (2021). Transition metal-promoted reactions in aqueous media and biological settings. Chemistry 27: 4789–4816, https://doi.org/10.1002/chem.202003927.Suche in Google Scholar PubMed

Dydio, P., Key, H.M., Nazarenko, A., Rha, J.Y.-E., Seyedkazemi, V., Clark, D.S., and Hartwig, J.F. (2016). An artificial metalloenzyme with the kinetics of native enzymes. Science 354: 102–106, https://doi.org/10.1126/science.aah4427.Suche in Google Scholar PubMed

Hassan, I.S., Ta, A.N., Danneman, M.W., Semakul, N., Burns, M., Basch, C.H., Dippon, V.N., McNaughton, B.R., and Rovis, T. (2019). Asymmetric δ-lactam synthesis with a monomeric streptavidin artificial metalloenzyme. J. Am. Chem. Soc. 141: 4815–4819, https://doi.org/10.1021/jacs.9b01596.Suche in Google Scholar PubMed PubMed Central

Huang, J., Liu, Z., Bloomer, B.J., Clark, D.S., Mukhopadhyay, A., Keasling, J.D., and Hartwig, J.F. (2020). Artificial biosynthetic pathway for an unnatural terpenoid with an iridium containing P450. ChemRxiv: 1–11.10.26434/chemrxiv.11955174Suche in Google Scholar

Jeong, W.J., Yu, J., and Song, W.J. (2020). Proteins as diverse, efficient, and evolvable scaffolds for artificial metalloenzymes. Chem. Commun. 56: 9586–9599, https://doi.org/10.1039/d0cc03137b.Suche in Google Scholar PubMed

Jeschek, M., Reuter, R., Heinisch, T., Trindler, C., Klehr, J., Panke, S., and Ward, T.R. (2016). Directed evolution of artificial metalloenzymes for in vivo metathesis. Nature 537: 661–665, https://doi.org/10.1038/nature19114.Suche in Google Scholar PubMed

Karayilan, M., Brezinski, W.P., Clary, K.E., Lichtenberger, D.L., Glass, R.S., and Pyun, J. (2019). Catalytic metallopolymers from [2Fe-2S] clusters: artificial metalloenzymes for hydrogen production. Angew. Chem. Int. Ed. 58: 7537–7550, https://doi.org/10.1002/anie.201813776.Suche in Google Scholar PubMed

Klein, A.S. and Zeymer, C. (2021). Design and engineering of artificial metalloproteins: from de novo metal coordination to catalysis. Protein Eng. Des. Sel. 34: 1–9, https://doi.org/10.1093/protein/gzab003.Suche in Google Scholar PubMed

Komiyama, M. and Ariga, K. (2019). Nanoarchitectonics to prepare practically useful artificial enzymes. Mol. Catal. 475: 110492, https://doi.org/10.1016/j.mcat.2019.110492.Suche in Google Scholar

Korendovych, I.V. and DeGrado, W.F. (2020). De novo protein design, a retrospective. Q. Rev. Biophys. 53: 1–33, https://doi.org/10.1017/S0033583519000131.Suche in Google Scholar PubMed PubMed Central

Large, B., Baranska, N.G., Booth, R.L., Wilson, K.S., and Duhme-Klair, A.K. (2021). Artificial metalloenzymes: the powerful alliance between protein scaffolds and organometallic catalysts. Curr. Opin. Green Sustain. Chem. 28: 100420, https://doi.org/10.1016/j.cogsc.2020.100420.Suche in Google Scholar

Lewis, J.C. (2019). Beyond the second coordination sphere: engineering dirhodium artificial metalloenzymes to enable protein control of transition metal catalysis. Acc. Chem. Res. 52: 576–584, https://doi.org/10.1021/acs.accounts.8b00625.Suche in Google Scholar PubMed

Liang, A.D., Serrano-Plana, J., Peterson, R.L., and Ward, T.R. (2019). Artificial metalloenzymes based on the biotin-streptavidin technology: enzymatic cascades and directed evolution. Acc. Chem. Res. 52: 585–595, https://doi.org/10.1021/acs.accounts.8b00618.Suche in Google Scholar PubMed PubMed Central

Lombardi, A., Pirro, F., Maglio, O., Chino, M., and DeGrado, W.F. (2019). De novo design of four-helix bundle metalloproteins: one scaffold, diverse reactivities. Acc. Chem. Res. 52: 1148–1159, https://doi.org/10.1021/acs.accounts.8b00674.Suche in Google Scholar PubMed PubMed Central

Loskot, S.A., Romney, D.K., Arnold, F.H., and Stoltz, B.M. (2017). Enantioselective total synthesis of nigelladine a via late-stage C–H oxidation enabled by an engineered P450 enzyme. J. Am. Chem. Soc. 139: 10196–10199, https://doi.org/10.1021/jacs.7b05196.Suche in Google Scholar PubMed PubMed Central

Mirts, E.N., Bhagi-Damodaran, A., and Lu, Y. (2019). Understanding and modulating metalloenzymes with unnatural amino acids, non-native metal ions, and non-native metallocofactors. Acc. Chem. Res. 52: 935–944, https://doi.org/10.1021/acs.accounts.9b00011.Suche in Google Scholar PubMed PubMed Central

Mukherjee, P. and Maiti, D. (2020). Evolution of strept(avidin)-based artificial metalloenzymes in organometallic catalysis. Chem. Commun. 56: 14519–14540, https://doi.org/10.1039/d0cc05450j.Suche in Google Scholar PubMed

Natoli, S.N. and Hartwig, J.F. (2019). Noble-metal substitution in hemoproteins: an emerging strategy for abiological catalysis. Acc. Chem. Res. 52: 326–335, https://doi.org/10.1021/acs.accounts.8b00586.Suche in Google Scholar PubMed

Oerlemans, R.A.J.F., Timmermans, S.B.P.E., and van Hest, J. (2021). Artificial organelles: towards adding or restoring intracellular activity. ChemBioChem 22: 1–29, https://doi.org/10.1002/cbic.202000850.Suche in Google Scholar PubMed PubMed Central

Oohora, K., Onoda, A., and Hayashi, T. (2019). Hemoproteins reconstituted with artificial metal complexes as biohybrid catalysts. Acc. Chem. Res. 52: 945–954, https://doi.org/10.1021/acs.accounts.8b00676.Suche in Google Scholar PubMed

Pagar, A.D., Patil, M.D., Flood, D.T., Yoo, T.H., Dawson, P.E., and Yun, H. (2021). Recent advances in biocatalysis with chemical modification and expanded amino acid alphabet. Chem. Rev. 121: 6173–6245, https://doi.org/10.1021/acs.chemrev.0c01201.Suche in Google Scholar PubMed

Perez-Rizquez, C., Rodriguez-Otero, A., and Palomo, J.M. (2019). Combining enzymes and organometallic complexes: novel artificial metalloenzymes and hybrid systems for C–H activation chemistry. Org. Biomol. Chem. 17: 7114–7123, https://doi.org/10.1039/c9ob01091b.Suche in Google Scholar PubMed

Pinter, T.B.J., Koebke, K.J., and Pecoraro, V.L. (2020). Catalysis and electron transfer in de novo designed helical scaffolds. Angew. Chem. Int. Ed. 59: 7678–7699, https://doi.org/10.1002/anie.201907502.Suche in Google Scholar PubMed PubMed Central

Poppe, L. and Vértessy, B.G. (2018). The fourth wave of biocatalysis emerges—the 13th international symposium on biocatalysis and biotransformations. ChemBioChem 19: 284–287, https://doi.org/10.1002/cbic.201700687.Suche in Google Scholar PubMed

Reetz, M.T. (2019). Directed evolution of artificial metalloenzymes: a universal means to tune the selectivity of transition metal catalysts? Acc. Chem. Res. 52: 336–344, https://doi.org/10.1021/acs.accounts.8b00582.Suche in Google Scholar PubMed

Roelfes, G. (2019). LmrR: a privileged scaffold for artificial metalloenzymes. Acc. Chem. Res. 52: 545–556, https://doi.org/10.1021/acs.accounts.9b00004.Suche in Google Scholar PubMed PubMed Central

Schwizer, F., Okamoto, Y., Heinisch, T., Gu, Y., Pellizzoni, M.M., Lebrun, V., Reuter, R., Kö, V., Lewis, J.C., and Ward, T.R. (2018). Artificial metalloenzymes: reaction scope and optimization strategies. Chem. Rev. 118: 142–231, https://doi.org/10.1021/acs.chemrev.7b00014.Suche in Google Scholar PubMed

Scinto, S.L., Bilodeau, D.A., Hincapie, R., Lee, W., Nguyen, S.S., Xu, M., Ende, C.W., Finn, M.G., Lang, K., Lin, Q., et al.. (2021). Bioorthogonal chemistry. Nat. Rev. Methods Prim. 1: 1–23, https://doi.org/10.1038/s43586-021-00028-z.Suche in Google Scholar PubMed PubMed Central

Serafim, L.F., Wang, L., Rathee, P., Yang, J., Frenk Knaul, H.S., and Prabhakar, R. (2021). Remediation of environmentally hazardous organophosphates by artificial metalloenzymes. Curr. Opin. Green Sustain. Chem. 100529, https://doi.org/10.1016/j.cogsc.2021.100529.Suche in Google Scholar

Sigman, J.A., Kwok, B.C., and Lu, Y. (2000). From myoglobin to heme-copper oxidase: design and engineering of a Cu(B) center into sperm whale myoglobin. J. Am. Chem. Soc. 122: 8192–8196, https://doi.org/10.1021/ja0015343.Suche in Google Scholar

Thompson, Z. and Cowan, J.A. (2020). Artificial metalloenzymes: recent developments and innovations in bioinorganic catalysis. Small 16: 2000392, https://doi.org/10.1002/smll.202000392.Suche in Google Scholar PubMed

Vallapurackal, J. (2021). Towards the directed evolution of artificial metalloenzymes. Chimia (Aarau) 75: 257–260, https://doi.org/10.2533/chimia.2021.257.Suche in Google Scholar PubMed

Vornholt, T. and Jeschek, M. (2020). The quest for xenobiotic enzymes: from new enzymes for chemistry to a novel chemistry of life. ChemBioChem 21: 2241–2249, https://doi.org/10.1002/cbic.202000121.Suche in Google Scholar PubMed

Ward Group. (2021). Artificial metalloenzymes publications @, Available at: https://amp.ward-lab.ch/.Suche in Google Scholar

Wilson, M.E. and Whitesides, G.M. (1978). Conversion of a protein to a homogeneous asymmetric hydrogenation catalyst by site-specific modification with a diphosphinerhodium(I) moiety. J. Am. Chem. Soc. 100: 306–307, https://doi.org/10.1021/ja00469a064.Suche in Google Scholar

Yamamura, K., and Kaiser, E.T. (1976). Studies on the oxidase activity of copper(II) carboxypeptidase A. J. Chem. Soc. Chem. Commun. 20: 830–831, https://doi.org/10.1039/c39760000830.Suche in Google Scholar

Yu, Y., Hu, C., Xia, L., and Wang, J. (2018). Artificial metalloenzyme design with unnatural amino acids and non-native cofactors. ACS Catal. 8: 1851–1863, https://doi.org/10.1021/acscatal.7b03754.Suche in Google Scholar

Yu, Y., Liu, X., and Wang, J. (2019). Expansion of redox chemistry in designer metalloenzymes. Acc. Chem. Res. 52: 557–565, https://doi.org/10.1021/acs.accounts.8b00627.Suche in Google Scholar PubMed

Zhang, R.K., Huang, X., and Arnold, F.H. (2019). Selective C–H bond functionalization with engineered heme proteins: new tools to generate complexity. Curr. Opin. Chem. Biol. 49: 67–75, https://doi.org/10.1016/j.cbpa.2018.10.004.Suche in Google Scholar PubMed PubMed Central

Zhou, Z. and Roelfes, G. (2020). Synergistic catalysis in an artificial enzyme by simultaneous action of two abiological catalytic sites. Nat. Catal. 3: 289–294, https://doi.org/10.1038/s41929-019-0420-6.Suche in Google Scholar
Received: 2021-07-23
Accepted: 2021-10-05
Published Online: 2021-10-18
Published in Print: 2022-03-28

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Chemical Biology in Drug Discovery
  3. Chemical biology in drug discovery
  4. Rational approaches towards inorganic and organometallic antibacterials
  5. Epithelial-mesenchymal transition and H2O2 signaling – a driver of disease progression and a vulnerability in cancers
  6. Covalent fragment-based ligand screening approaches for identification of novel ubiquitin proteasome system modulators
  7. Artificial metalloenzymes in a nutshell: the quartet for efficient catalysis
  8. Photochemical protein modification in complex biological environments: recent advances and considerations for future chemical methods development
  9. Using the yeast three-hybrid system for the identification of small molecule-protein interactions with the example of ethinylestradiol
  10. Expanded profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39
  11. Two-photon fluorescent turn-on probes for highly efficient detection and profiling of thiols in live cells and tissues
https://doi.org/10.1515/hsz-2021-0329
Schlagwörter für diesen Artikel
biocatalysis; in vivo catalysis; new-to-nature reactivity; protein engineering

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Chemical Biology in Drug Discovery
  3. Chemical biology in drug discovery
  4. Rational approaches towards inorganic and organometallic antibacterials
  5. Epithelial-mesenchymal transition and H2O2 signaling – a driver of disease progression and a vulnerability in cancers
  6. Covalent fragment-based ligand screening approaches for identification of novel ubiquitin proteasome system modulators
  7. Artificial metalloenzymes in a nutshell: the quartet for efficient catalysis
  8. Photochemical protein modification in complex biological environments: recent advances and considerations for future chemical methods development
  9. Using the yeast three-hybrid system for the identification of small molecule-protein interactions with the example of ethinylestradiol
  10. Expanded profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39
  11. Two-photon fluorescent turn-on probes for highly efficient detection and profiling of thiols in live cells and tissues
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2026 De Gruyter Brill
Heruntergeladen am 30.1.2026 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2021-0329/html
Button zum nach oben scrollen