Carbonic anhydrase II as host protein for the creation of a biocompatible artificial metathesase

Zhao, Jingming; Kajetanowicz, Anna; Ward, Thomas R.

doi:10.1039/c5ob00428d

Cited by 49 publications

(40 citation statements)

References 26 publications

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“…To our knowledge this was the first example of crossmetathesis using an ArM (Table 19). An artificial metathase based on on human carbonic anhydrase II (hCA II) was reported by Ward et al 347 The hCA II protein has a strong affinity (typically nM -pM) toward arylsulfonamides due to sulfonamide coordination to an active site zinc ion. Three different sulfonamide-substituted catalysts were prepared (159)(160)(161), and their activity toward ring closing metathesis of substrate 147 was evaluated.…”

Section: Scheme 50mentioning

confidence: 99%

Artificial Metalloenzymes: Reaction Scope and Optimization Strategies

et al. 2017

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The incorporation of a synthetic, catalytically competent metallocofactor into a protein scaffold to generate an artificial metalloenzyme (ArM) has been explored since the late 1970's. Progress in the ensuing years was limited by the tools available for both organometallic synthesis and protein engineering. Advances in both of these areas, combined with increased appreciation of the potential benefits of combining attractive features of both homogeneous catalysis and enzymatic catalysis, led to a resurgence of interest in ArMs starting in the early 2000's. Perhaps the most intriguing of potential ArM properties is their ability to endow homogeneous catalysts with a genetic memory. Indeed, incorporating a homogeneous catalyst into a genetically encoded scaffold offers the opportunity to improve ArM performance by directed evolution. This capability could, in turn, lead to improvements in ArM efficiency similar to those obtained for natural enzymes, providing systems suitable for practical applications and greater insight into the role of second coordination sphere interactions in organometallic catalysis. Since its renaissance in the early 2000's, different aspects of artificial metalloenzymes have been extensively reviewed and highlighted. Our intent is to provide a comprehensive overview of all work in the field up to December 2016, organized according to reaction class. Because of the wide range of non-natural reactions catalyzed by ArMs, this was done using a functional-group transformation classification. The review begins with a summary of the proteins and the anchoring strategies used to date for the creation of ArMs, followed by a historical perspective. Then follows a summary of the reactions catalyzed by ArMs and a concluding critical outlook. This analysis allows for comparison of similar reactions catalyzed by ArMs constructed using different metallocofactor anchoring strategies, cofactors, protein scaffolds, and mutagenesis strategies. These data will be used to construct a searchable Web site on ArMs that will be updated regularly by the authors.

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Section: Scheme 50mentioning

confidence: 99%

Artificial Metalloenzymes: Reaction Scope and Optimization Strategies

et al. 2017

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“…Different strategies, such as a combination of synthetic protein chemistry and molecular biology [5,6], dative coordination of an organometallic ligand to the metal in the protein scaffold [7] or by covalent incorporation with a specific group in the active site [8], have been employed.…”

Section: Introductionmentioning

confidence: 99%

Design of Heterogeneous Hoveyda–Grubbs Second-Generation Catalyst–Lipase Conjugates

2016

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Heterogeneous catalysts have been synthesized by the conjugation of Hoveyda-Grubbs second-generation catalyst with a lipase. The catalytic properties of the organometallic compound in solution were firstly optimized, evaluating the activity of Ru in the ring-closing metathesis of diethyldiallymalonate at 25 • C at different solvents and in the presence of different additives. The best result was found using tetrahydrofuran as a solvent. Some additives such as phenylboronic acid or polyetheneglycol slightly improved the activity of the Ru catalyst whereas others, such as pyridine or dipeptides affected it negatively. The organometallic compound immobilized on functionalized-surface materials activated with boronic acid or epoxy groups (around 50-60 µg per mg support) and showed 50% conversion at 24 h in the ring-closing metathesis. Cross-linked enzyme aggregates (CLEA's) of the Hoveyda-Grubbs second-generation catalyst with Candida antarctica lipase (CAL-B) were prepared, although low Ru catalyst was found to be translated in low conversion. Therefore, a sol-gel preparation of the Hoveyda-Grubbs second-generation and CAL-B was performed. This catalyst exhibited good activity in the metathesis of diethyldiallymalonate in toluene and in aqueous media. Finally, a new sustainable approach was used by the conjugation lipase-Grubbs in solid phase in aqueous media. Two strategies were used: one using lipase previously covalently immobilized on an epoxy-Sepharose support (hydrophilic matrix) and then conjugated with grubbs; and in the second, the free lipase was incubated with organometallic in aqueous solution and then immobilized on epoxy-Sepharose. The different catalysts showed excellent conversion values in the ring-closing metathesis of diethyldiallymalonate in aqueous media at 25 • C.

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“…In 2011, the first ArMs catalyzing olefin metathesis, artificial metathases, were reported by Ward and Hilvert, respectively [ 103 , 104 ]. As the abiotic cofactor, a second-generation Grubbs–Hoveyda (GH) catalyst possessing an anchoring moiety was utilized in these studies, as well as in subsequent reports from other research groups [ 105 , 106 , 107 , 108 , 109 , 110 ].…”

Section: Cascade Sequential and Synergetic Reactionsmentioning

confidence: 99%

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

Himiyama

Okamoto

2020

Molecules

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Artificial metalloenzymes (ArMs) comprise a synthetic metal complex in a protein scaffold. ArMs display performances combining those of both homogeneous catalysts and biocatalysts. Specifically, ArMs selectively catalyze non-natural reactions and reactions inspired by nature in water under mild conditions. In the past few years, the construction of ArMs that possess a genetically incorporated unnatural amino acid and the directed evolution of ArMs have become of great interest in the field. Additionally, biochemical applications of ArMs have steadily increased, owing to the fact that compartmentalization within a protein scaffold allows the synthetic metal complex to remain functional in a sea of inactivating biomolecules. In this review, we present updates on: (1) the newly reported ArMs, according to their type of reaction, and (2) the unique biochemical applications of ArMs, including chemoenzymatic cascades and intracellular/in vivo catalysis. We believe that ArMs have great potential as catalysts for organic synthesis and as chemical biology tools for pharmaceutical applications.

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Carbonic anhydrase II as host protein for the creation of a biocompatible artificial metathesase

Cited by 49 publications

References 26 publications

Artificial Metalloenzymes: Reaction Scope and Optimization Strategies

Artificial Metalloenzymes: Reaction Scope and Optimization Strategies

Design of Heterogeneous Hoveyda–Grubbs Second-Generation Catalyst–Lipase Conjugates

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

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