Artificial metalloenzyme

Edit links
From Wikipedia, the free encyclopedia

An artificial metalloenzyme (ArM) is a metalloprotein made in the laboratory which cannot be found in the nature and can catalyze certain desired chemical reactions.[1][2] Despite fitting into classical enzyme categories, ArMs also have potential in chemical reactivity like catalyzing Suzuki coupling,[3] metathesis[4] and so on, which are never reported in natural enzymatic reaction. With the progress in organometallic synthesis and protein engineering, more and more new kind of design of ArMs came out, showing promising future in both academia and industrial aspects.[5]

In 2018, one half of the Nobel Prize in Chemistry was awarded to Frances H. Arnold “for the directed evolution of enzymes”, which elegantly evolved the artificial metalloenzymes to realize efficient and highly selective abiotic chemical reaction in vitro and in vivo.

Origin[edit]

Dated back to 1956, the first protein modified transition metal catalyst was documented.[6] The Palladium(II) salt was absorbed onto silk fibroin fiber, reduced by hydrogen to get the first reported ArM, which can catalyze asymmetric hydrogenation.

Pd-silk fibroin complex catalyzed asymmetric hydrogenation

First attempt to anchor an abiotic metal center onto a protein was reported by Whitesides using biotin-avidin interaction, making an artificial hydrogenase.[7] The presence of avidin can significantly increase the catalytic capacity of Rhodium(I) cofactor in aqueous phosphate buffer.

First biotinylated ArM catalyzed hydrogenation.

Formation[edit]

Abiotic cofactor anchoring[edit]

There are four main types of making to localize the artificial metal cofactor to make an ArM, including covalent, supramolecular, metal substitution and dative.[5]

Covalent[edit]

With the development of bioconjugation technology, there are plenty of options to covalently ligating an artificial metal cofactor onto a protein: i) cysteine residue based chemistry like: Cys-meleimide,[8] Cys-α-haloketone,[9] Cys-benzylhalide chemistry and disulfide formation,[10] ii) post-translational bioorthogonal modification based on Amber suppression (e.g., Click chemistry)[11] and iii) enzyme active site modification (e.g., covalent bond formation between lipase and lipase inhibitor).[12]

Different approaches to anchoring artificial metal cofactors. (Ball: Protein; Square: Metal cofactors)

The video shows an example using reaction between cysteine residue and α-haloketone to introduce a phenanthroline ligand into an adipocyte lipid binding protein.[9] In this context, the ArM can selectively hydrolyze certain racemic esters.

An artificial oxidase based on Cu(II)-bipyridine complex linked to the cysteine in the active site of adipocyte lipid binding protein (PDB: 1A18). Artificial ligand showed in red (copper not shown).

Supramolecular[edit]

Avidin and biotinylated artificial metal cofactor the most commonly used supramolecular strategy to make an ArM.[13] In the example showed below, the ligand of Ru(I) complex was modified with biotin and than the whole complex was loaded onto streptavidin by biotin-avidin interaction. The resulted ArM can catalyze the reduction of prochiral ketones. Taking advantages of protein context, different mutants of strepavidin can achieve different stereochemistry selectivity by direct evolution. For example, Mutant L124V can selectively reduce certain ketone into R-alcohol while S112A-K121N can reduce the same substance into S-alcohol.

An ArM using biotin-streptavidin interaction to anchor artificial metal cofactor (PDB: 2QCB)

Besides biotin-avidin based ArMs, another important attempt utilizing supuramolecular interaction is antigen-antibody recognition. First reported in 1989 by Lerner, a monoclonal antibody-based ArM is raised to hydrolyze specific peptide.[14]

Metal substitution[edit]

Natural metal ion cofactor center was substituted by non-native metal to achieve unique reactivity.[15]

Metal substitution in a natural cofactor

Dative[edit]

The dative anchoring strategy uses natural amino acid residue in the protein like His, Cys, Glu, Asp and Ser to coordinate to a metal center. Like the first example of Pd-fibroin, dative anchoring is not commonly used now and often resulted in a more ambiguous binding site for metal compared with previous three methods.

Protein backbone and Evolution[edit]

In addition to anchoring artificial metal center on a protein, researchers like Frances Arnold also focused on changing the native environment of natural metal cofactor. Due to the protein context in which the metal catalytic center located, ArMs have a large sequence space to evolve to meet different demands on substance specificity and regio- and enantioselectivity. Directed evolution was used to tailor the catalytic capacity and repurpose the enzyme function. Mostly based on native porphyrin-metal cofactor, Arnold's lab has developed many ArMs has unique ArMs to catalyze regioselective and/or enantioselective Carbon-Boron bond formation,[16] carbene insertion,[17] and aminohydroxylation[18] by evolving the sequence context of the corresponding ArMs.

Function[edit]

An evolvable aqueous asymmetric catalysts[edit]

As a catalyst, ArMs have three advantages,

  1. thanks to the development in molecular biology, it is quite easy to generate a library of ArM mutants which has a size up to 108. Using proper selection method, the ArM has a large potential to gain unique catalytic properties.
  2. ArMs are proteins, it can have both hydrophilic and hydrophobic surface in the aqueous solution. Anchoring the artificial cofactor which is not easily dissolve in water would help it function in aqueous phase. In some structure, the hydrophobic cavity would protect some labile bond (like many carbene or nitrene-metal complex in Arnold ArMs).
  3. The backbone itself in ArM is a asymmetric environment. In some cases, the enantioselective synthesis can be tuned by changing one or two amino acid residues around the metal catalytic center.[13]

So far, ArMs can catalyze a lot of chemical reactions, such as: allylic alkylation, allylic amination, aldol reaction, alcohol oxidation, C-H activation,[19] click reaction,[20] catechol oxidation, CO2 reduction, cyclopropanation,[21] Diels-Alder reaction,[22] epoxidation, epoxide ring opening, Friedel-Crafts alkylation,[23] hydrogenation, hydroformylation, Heck reaction, metathesis,[4] Michael addition, nitrite reduction, NO reduction, Suzuki reaction,[3] Si-H insertion,[24] polymerization (atom transfer radical polymerization).[25]

References[edit]

  1. ^ Morra S, Pordea A (October 2018). "Biocatalyst-artificial metalloenzyme cascade based on alcohol dehydrogenase". Chemical Science. 9 (38). Royal Society of Chemistry: 7447–7454. doi:10.1039/C8SC02371A. PMC 6180310. PMID 30319745.
  2. ^ Leurs M, Dorn B, Wilhelm S, Manisegaran M, Tiller JC (July 2018). "Multicore Artificial Metalloenzymes Derived from Acylated Proteins as Catalysts for the Enantioselective Dihydroxylation and Epoxidation of Styrene Derivatives". Chemistry: A European Journal. 24 (42): 10859–10867. doi:10.1002/chem.201802185. PMID 29808506.
  3. ^ a b Chatterjee A, Mallin H, Klehr J, Vallapurackal J, Finke AD, Vera L, Marsh M, Ward TR (January 2016). "An enantioselective artificial Suzukiase based on the biotin-streptavidin technology". Chemical Science. 7 (1): 673–677. doi:10.1039/C5SC03116H. PMC 5953008. PMID 29896353.
  4. ^ a b Jeschek M, Reuter R, Heinisch T, Trindler C, Klehr J, Panke S, Ward TR (September 2016). "Directed evolution of artificial metalloenzymes for in vivo metathesis" (PDF). Nature. 537 (7622): 661–665. Bibcode:2016Natur.537..661J. doi:10.1038/nature19114. PMID 27571282. S2CID 205250261.
  5. ^ a b Schwizer F, Okamoto Y, Heinisch T, Gu Y, Pellizzoni MM, Lebrun V, Reuter R, Köhler V, Lewis JC, Ward TR (January 2018). "Artificial Metalloenzymes: Reaction Scope and Optimization Strategies" (PDF). Chemical Reviews. 118 (1): 142–231. doi:10.1021/acs.chemrev.7b00014. PMID 28714313.
  6. ^ Akabori S, Sakurai S, Izumi Y, Fujii Y (August 1956). "An Asymmetric Catalyst". Nature. 178 (4528): 323–324. Bibcode:1956Natur.178..323A. doi:10.1038/178323b0. ISSN 0028-0836. PMID 13358737. S2CID 4221816.
  7. ^ Wilson ME, Whitesides GM (January 1978). "Conversion of a protein to a homogeneous asymmetric hydrogenation catalyst by site-specific modification with a diphosphinerhodium(I) moiety". Journal of the American Chemical Society. 100 (1): 306–307. doi:10.1021/ja00469a064. ISSN 0002-7863.
  8. ^ Onoda A, Kihara Y, Fukumoto K, Sano Y, Hayashi T (August 2014). "Photoinduced Hydrogen Evolution Catalyzed by a Synthetic Diiron Dithiolate Complex Embedded within a Protein Matrix". ACS Catalysis. 4 (8): 2645–2648. doi:10.1021/cs500392e.
  9. ^ a b Davies RR, Distefano A (December 1997). "A Semisynthetic Metalloenzyme Based on a Protein Cavity That Catalyzes the Enantioselective Hydrolysis of Ester and Amide Substrates". Journal of the American Chemical Society. 119 (48): 11643–11652. doi:10.1021/ja970820k. ISSN 0002-7863.
  10. ^ Platis IE, Ermácora MR, Fox RO (November 1993). "Oxidative polypeptide cleavage mediated by EDTA-Fe covalently linked to cysteine residues". Biochemistry. 32 (47): 12761–7. doi:10.1021/bi00210a027. PMID 8251497.
  11. ^ Yang H, Srivastava P, Zhang C, Lewis JC (January 2014). "A general method for artificial metalloenzyme formation through strain-promoted azide-alkyne cycloaddition". ChemBioChem. 15 (2): 223–7. doi:10.1002/cbic.201300661. PMC 3996923. PMID 24376040.
  12. ^ Kruithof CA, Casado MA, Guillena G, Egmond MR, van der Kerk-van Hoof A, Heck AJ, Klein Gebbink RJ, van Koten G (November 2005). "Lipase active-site-directed anchoring of organometallics: metallopincer/protein hybrids". Chemistry: A European Journal. 11 (23): 6869–77. doi:10.1002/chem.200500671. PMID 16224766.
  13. ^ a b Creus M, Pordea A, Rossel T, Sardo A, Letondor C, Ivanova A, Letrong I, Stenkamp RE, Ward TR (2008). "X-ray structure and designed evolution of an artificial transfer hydrogenase". Angewandte Chemie. 47 (8): 1400–4. doi:10.1002/anie.200704865. PMID 18176932.
  14. ^ Iverson BL, Lerner RA (March 1989). "Sequence-specific peptide cleavage catalyzed by an antibody". Science. 243 (4895): 1184–8. Bibcode:1989Sci...243.1184I. doi:10.1126/science.2922606. PMID 2922606.
  15. ^ Kandemir B, Chakraborty S, Guo Y, Bren KL (January 2016). "Semisynthetic and Biomolecular Hydrogen Evolution Catalysts". Inorganic Chemistry. 55 (2): 467–77. doi:10.1021/acs.inorgchem.5b02054. PMID 26671416.
  16. ^ Chen K, Huang X, Zhang SQ, Zhou AZ, Kan SB, Hong X, Arnold FH (March 2019). "c-Catalyzed Lactone-Carbene B-H Insertion". Synlett. 30 (4): 378–382. doi:10.1055/s-0037-1611662. PMC 6436545. PMID 30930550.
  17. ^ Brandenberg OF, Chen K, Arnold FH (May 2019). "Directed Evolution of a Cytochrome P450 Carbene Transferase for Selective Functionalization of Cyclic Compounds" (PDF). Journal of the American Chemical Society. 141 (22): 8989–8995. doi:10.1021/jacs.9b02931. PMID 31070908.
  18. ^ Cho I, Prier CK, Jia ZJ, Zhang RK, Görbe T, Arnold FH (March 2019). "Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein". Angewandte Chemie. 58 (10): 3138–3142. doi:10.1002/anie.201812968. PMID 30600873.
  19. ^ Dydio P, Key HM, Nazarenko A, Rha JY, Seyedkazemi V, Clark DS, Hartwig JF (October 2016). "An artificial metalloenzyme with the kinetics of native enzymes". Science. 354 (6308): 102–106. Bibcode:2016Sci...354..102D. doi:10.1126/science.aah4427. PMID 27846500.
  20. ^ Yokoi N, Inaba H, Terauchi M, Stieg AZ, Sanghamitra NJ, Koshiyama T, Yutani K, Kanamaru S, Arisaka F, Hikage T, Suzuki A, Yamane T, Gimzewski JK, Watanabe Y, Kitagawa S, Ueno T (September 2010). "Construction of robust bio-nanotubes using the controlled self-assembly of component proteins of bacteriophage T4". Small. 6 (17): 1873–9. doi:10.1002/smll.201000772. PMID 20661999.
  21. ^ Key HM, Dydio P, Clark DS, Hartwig JF (June 2016). "Abiological catalysis by artificial haem proteins containing noble metals in place of iron". Nature. 534 (7608): 534–7. Bibcode:2016Natur.534..534K. doi:10.1038/nature17968. PMID 27296224. S2CID 205249065.
  22. ^ Podtetenieff J, Taglieber A, Bill E, Reijerse EJ, Reetz MT (July 2010). "An artificial metalloenzyme: creation of a designed copper binding site in a thermostable protein". Angewandte Chemie. 49 (30): 5151–5. doi:10.1002/anie.201002106. PMID 20572232.
  23. ^ Drienovská I, Rioz-Martínez A, Draksharapu A, Roelfes G (January 2015). "in vivo incorporation of metal-binding unnatural amino acids". Chemical Science. 6 (1): 770–776. doi:10.1039/C4SC01525H. PMC 5590542. PMID 28936318.
  24. ^ Arnold FH (April 2018). "Directed Evolution: Bringing New Chemistry to Life". Angewandte Chemie. 57 (16): 4143–4148. doi:10.1002/anie.201708408. PMC 5901037. PMID 29064156.
  25. ^ Renggli K, Nussbaumer MG, Urbani R, Pfohl T, Bruns N (January 2014). "A chaperonin as protein nanoreactor for atom-transfer radical polymerization". Angewandte Chemie. 53 (5): 1443–7. doi:10.1002/anie.201306798. PMID 24459061.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Artificial_metalloenzyme&oldid=1185533316"