Genetically engineered proteins with two active sites for enhanced biocatalysis and synergistic chemo- and biocatalysis

Alonso, Sandra; Santiago, Gerard; Cea-Rama, Isabel; Fernández-López, Laura; Coscolín, Cristina; Modregger, Jan; Ressmann, Anna K.; Martínez-Martínez, Mónica; Marrero, Helena; Bargiela, Rafael; Pita, Marcos; Gonzalez, Jose L. Ugia; Briand, Manon L.; Rojo, David; Barbas, Coral; Plou, Francisco J.; Golyshin, Peter N.; Shahgaldian, Patrick; Sanz‐Aparicio, Julia; Guallar, Vı́ctor; Ferrer, Manuel

doi:10.1038/s41929-019-0394-4

Cited by 99 publications

(141 citation statements)

References 40 publications

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“…Biocatalytic dehalogenation on the basis of microorganisms typically operates under mild temperatures and pressures with fewer hazardous solvents in comparison of physicochemical transformations and plays a crucial role in achieving the sustainable development goals 12 . However, biocatalytic systems are time-consuming and incapable of degrading refractory and toxic pollutants completely 13 – 15 . To bridge nature’s catalytic repertoire and the demands of sustainable and effective environmental remediation, chemists have started to import function of microbial enzymes into chemical materials.…”

Section: Introductionmentioning

confidence: 99%

Integrating single-cobalt-site and electric field of boron nitride in dechlorination electrocatalysts by bioinspired design

et al. 2021

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The construction of enzyme-inspired artificial catalysts with enzyme-like active sites and microenvironment remains a great challenge. Herein, we report a single-atomic-site Co catalyst supported by carbon doped boron nitride (BCN) with locally polarized B–N bonds (Co SAs/BCN) to simulate the reductive dehalogenases. Density functional theory analysis suggests that the BCN supports, featured with ionic characteristics, provide additional electric field effect compared with graphitic carbon or N-doped carbon (CN), which could facilitate the adsorption of polarized organochlorides. Consistent with the theoretical results, the Co SAs/BCN catalyst delivers a high activity with nearly complete dechlorination (~98%) at a potential of −0.9 V versus Ag/AgCl for chloramphenicol (CAP), showing that the rate constant (k) contributed by unit mass of metal (k/ratio) is 4 and 19 times more active than those of the Co SAs/CN and state-of-the-art Pd/C catalyst, respectively. We show that Co single atoms coupled with BCN host exhibit high stability and selectivity in CAP dechlorination and suppress the competing hydrogen evolution reaction, endowing the Co SAs/BCN as a candidate for sustainable conversion of organic chloride.

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Section: Introductionmentioning

confidence: 99%

Integrating single-cobalt-site and electric field of boron nitride in dechlorination electrocatalysts by bioinspired design

et al. 2021

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“…It is an arduous task that does not involve knowledge of what determines new activity, and the quality of the said starting point is unknown since iterative rounds of mutagenesis target sites scattered throughout the global protein structure 37 . An alternative avenue in engineering existing enzymes has proven successful in enhancing our ability to recognize the origin of enzymes' remarkable performances using theoretical and computational methods [38][39][40][41][42][43] . By exploring a small fraction of the vast sequence space, successful examples of studies focused on reshaping active sites that accommodate individual substrates have been reported [44][45][46][47] .…”

Section: Discussionmentioning

confidence: 99%

Development of a versatile and efficient C-N lyase platform for asymmetric hydroamination via computational enzyme redesign

Cui¹,

Wang²,

Bu³

et al. 2020

Preprint

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Although C-N bonds are ubiquitous in natural products, pharmaceuticals, and agrochemicals, biocatalysts that forge these bonds with high atom efficiency and enantioselectivity have primarily been limited to a few select enzymes. In particular, the use of ammonia lyases has emerged as a powerful strategy to access C-N bond formation through hydroamination reactions, which has no counterpart in traditional synthetic chemistry. However, the broad utility of ammonia lyases is rather restricted due to their narrow synthetic scope, and the conjugate addition of a matrix of nucleophilic donors to electrophilic acceptors remains a longstanding challenge. Herein, we report the computational redesign of aspartase, a highly specific ammonia lyase, to yield C-N lyases with unprecedented cross-compatibility of nonnative nucleophiles and electrophiles. A wide range of noncanonical amino acids (ncAAs) are afforded with excellent conversion (up to 99%), regioselectivity > 99%, and product enantiomeric excess > 99%, and the process is scalable under industrially relevant protocols (demonstrated in kilogram-scale synthesis). Furthermore, the redesigned enzymes can be facilely integrated in cascade reactions, as we demonstrated the synthesis of β-lactams with different substitution patterns at the N-1 and C-4 positions in a one-pot reaction. This versatile and efficient C-N lyase platform supports the preparation of diverse libraries of ncAAs and their derivatives and will present opportunities in medicinal chemistry and synthetic biology.

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“…For example, several new strategies have been published, such as the design of plurizymes (enzymes bearing a natural and an artificially designed active center), the design of irreversible inhibitors directed to one of these active center bearing a metal catalytic center and the use of modified plurizymes (bearing a free active center while the other active center presented the inhibitor with a metal catalysts) in a cascade reaction. 109 Immobilization was the initial answer to the problem of enzyme solubility, which complicates the reuse of enzymes. 106,110,111 Currently, with the decreasing price of enzymes, enzyme immobilization should address many other enzyme limitations, such as improving activity, stability, selectivity and specificity, decreasing inhibition 104 or purifying the enzyme.…”

Section: Glucose Oxidase Immobilizationmentioning

confidence: 99%

Enzyme production ofd-gluconic acid and glucose oxidase: successful tales of cascade reactions

Kornecki

Carballares

Tardioli

et al. 2020

Catal. Sci. Technol.

102

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Genetically engineered proteins with two active sites for enhanced biocatalysis and synergistic chemo- and biocatalysis

Cited by 99 publications

References 40 publications

Integrating single-cobalt-site and electric field of boron nitride in dechlorination electrocatalysts by bioinspired design

Integrating single-cobalt-site and electric field of boron nitride in dechlorination electrocatalysts by bioinspired design

Development of a versatile and efficient C-N lyase platform for asymmetric hydroamination via computational enzyme redesign

Enzyme production ofd-gluconic acid and glucose oxidase: successful tales of cascade reactions

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