Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

Fujieda, Nobutaka; Ichihashi, H.; Yuasa, Miho; Nishikawa, Yosuke; Kurisu, Genji; Itoh, Shinobu

doi:10.1002/anie.202000129

Cited by 16 publications

(13 citation statements)

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“…The M8L mutation provided moderately improved activity and selectivity (99%), which were correlated to a hydrophobic interaction with Trp96, as described in a previous study vide supra . The Itoh group has reported a cupin-based catalyst using only natural amino acids (Figure b) . Starting from a natural (His) 4 binding motif, a ligand set library was screened by decreasing numbers of His residues.…”

Section: Activity Beyond the First Coordination Sphere In Engineered ...mentioning

confidence: 61%

“…The insets at the bottom demonstrate how the hydrogen bond with Cys106 changes the orientation of the substrate and thereby alters the product enantioselectivity. Reprinted with permission from refs and . Copyright 2020 Nature Publishing Group and Wiley-VCH.…”

Section: Activity Beyond the First Coordination Sphere In Engineered ...mentioning

confidence: 99%

“…The Itoh group has reported a cupin-based catalyst using only natural amino acids (Figure 43b). 496 Starting from a natural (His) 4 binding motif, a ligand set library was screened by decreasing numbers of His residues. Both the tris-His mutant H52A (S product) and the bis-His mutant H54A/H58A (R product) were found capable of catalyzing the Michael addition reaction with both high yield and selectivity, but interestingly, their enantioselectivities were reversed relative to one another.…”

Section: Designed Copper Enzymes With New-to-nature Activitiesmentioning

confidence: 99%

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Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

et al. 2022

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Metalloenzymes catalyze a variety of reactions using a limited number of natural amino acids and metallocofactors. Therefore, the environment beyond the primary coordination sphere must play an important role in both conferring and tuning their phenomenal catalytic properties, enabling active sites with otherwise similar primary coordination environments to perform a diverse array of biological functions. However, since the interactions beyond the primary coordination sphere are numerous and weak, it has been difficult to pinpoint structural features responsible for the tuning of activities of native enzymes. Designing artificial metalloenzymes (ArMs) offers an excellent basis to elucidate the roles of these interactions and to further develop practical biological catalysts. In this review, we highlight how the secondary coordination spheres of ArMs influence metal binding and catalysis, with particular focus on the use of native protein scaffolds as templates for the design of ArMs by either rational design aided by computational modeling, directed evolution, or a combination of both approaches. In describing successes in designing heme, nonheme Fe, and Cu metalloenzymes, heteronuclear metalloenzymes containing heme, and those ArMs containing other metal centers (including those with non-native metal ions and metallocofactors), we have summarized insights gained on how careful controls of the interactions in the secondary coordination sphere, including hydrophobic and hydrogen bonding interactions, allow the generation and tuning of these respective systems to approach, rival, and, in a few cases, exceed those of native enzymes. We have also provided an outlook on the remaining challenges in the field and future directions that will allow for a deeper understanding of the secondary coordination sphere a deeper understanding of the secondary coordintion sphere to be gained, and in turn to guide the design of a broader and more efficient variety of ArMs.

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Section: Activity Beyond the First Coordination Sphere In Engineered ...mentioning

confidence: 61%

Section: Activity Beyond the First Coordination Sphere In Engineered ...mentioning

confidence: 99%

Section: Designed Copper Enzymes With New-to-nature Activitiesmentioning

confidence: 99%

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Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

et al. 2022

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“…Highest activity and stereoselectiviy were obtained after protein engineering and a single mutation was sufficient to obtain excellent values (up to 99% ee for the ( S )-product with H52A). 230 …”

Section: Stereoselective Reactions Involving Transformations Of Sp 2 Carbonsmentioning

confidence: 99%

Enzymatic strategies for asymmetric synthesis

Hall

2021

RSC Chem. Biol.

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“…Previously, Roelfes and coworkers reported a DNA-based ArM as a catalyst for the Michael addition reaction [ 69 ]. Recently, Fujieda et al developed a protein-based ArM for this transformation [ 70 ]. As described above, their previous work on catalytic dihydroxylation with Os·TM-1459 proved that TM-1459 could be utilized as a ligand for metal ions [ 48 ].…”

Section: Recent Progress On the Various Reactions Catalyzed By Armmentioning

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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Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

Cited by 16 publications

References 46 publications

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

Enzymatic strategies for asymmetric synthesis

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

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