Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(5), P. 1209 - 1225

Published: Jan. 25, 2021

ConspectusDespite the astonishing diversity of naturally occurring biocatalytic processes, enzymes do not catalyze many transformations favored by synthetic chemists. Either nature does care about specific products, or if she does, has adopted a different strategy. In cases, appropriate reagents used chemists are readily accessible to biological systems. Here, we discuss our efforts expand catalytic repertoire encompass powerful reactions previously known only in small-molecule catalysis: formation and transfer reactive carbene nitrene intermediates leading broad range including products with bonds biology. light structural similarity iron (Fe═C(R1)(R2)) (Fe═NR) oxo (Fe═O) intermediate involved cytochrome P450-catalyzed oxidation, have precursors that systems encountered repurposed P450s natural world. The resulting protein catalysts fully genetically encoded function intact microbial cells cell-free lysates, where their performance can be improved optimized directed evolution. By leveraging promiscuity P450 enzymes, evolved transferases exhibiting excellent activity toward these new-to-nature reactions. Since initial report 2012, number other heme proteins myoglobins, protoglobins, cytochromes c also been found engineered promote unnatural transfer. Due altered active-site environments, often displayed complementary activities selectivities P450s.Using wild-type proteins, others described selective reactions, cyclopropanation, cyclopropenation, Si–H insertion, B–H C–H insertion. Similarly, variety asymmetric processes aziridination, sulfide imidation, amidation, and, most recently, amination demonstrated. scopes state-of-the-art based on transition-metal catalysts, making biocatalysts valuable addition chemist's toolbox. Moreover, enabled exquisite regio- stereocontrol imposed enzyme catalyst, this platform provides an exciting opportunity address challenging problems modern chemistry catalysis, ones eluded for decades.

Language: Английский

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Exploiting attractive non-covalent interactions for the enantioselective catalysis of reactions involving radical intermediates

Nature Chemistry, Journal Year: 2020, Volume and Issue: 12(11), P. 990 - 1004

Published: Oct. 19, 2020

Language: Английский

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Single-atom nanozymes catalytically surpassing naturally occurring enzymes as sustained stitching for brain trauma

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 12, 2022

Regenerable nanozymes with high catalytic stability and sustainability are promising substitutes for naturally-occurring enzymes but limited by insufficient non-selective activities. Herein, we developed single-atom of RhN

Language: Английский

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Iron- and cobalt-catalyzed C(sp³)–H bond functionalization reactions and their application in organic synthesis

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(15), P. 5310 - 5358

Published: Jan. 1, 2020

This review highlights the developments in iron and cobalt catalyzed C(sp³)–H bond functionalization reactions with emphasis on their applications organic synthesis, i.e. natural products pharmaceuticals synthesis and/or modification.

Language: Английский

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

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(14), P. 11974 - 12045

Published: July 11, 2022

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

Language: Английский

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Microbial enzymes will offer limited solutions to the global plastic pollution crisis

Microbial Biotechnology, Journal Year: 2022, Volume and Issue: 16(2), P. 195 - 217

Published: Sept. 13, 2022

Global economies depend on the use of fossil-fuel-based polymers with 360-400 million metric tons synthetic being produced per year. Unfortunately, an estimated 60% global production is disposed into environment. Within this framework, microbiologists have tried to identify plastic-active enzymes over past decade. Until now, research has largely failed deliver functional biocatalysts acting commodity such as polyethylene (PE), polypropylene (PP), polyvinylchloride (PVC), ether-based polyurethane (PUR), polyamide (PA), polystyrene (PS) and rubber (SR). However, few are known act low-density low-crystalline (amorphous) terephthalate (PET) ester-based PUR. These above-mentioned represent >95% all plastics produced. Therefore, main challenge currently facing in finding polymer-active targeting majority plastics. identifying either implement them biotechnological processes or understand their potential role nature emerging field. The application these still its infancy. Here, we summarize current knowledge microbial enzymes, distribution impact plastic degradation industrial nature. We further outline major challenges novel optimizing ones by approaches problems arising through falsely annotated unfiltered database entries. Finally, highlight applications possible re- upcycling concepts using microorganisms.

Language: Английский

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Opportunities and Challenges for Machine Learning-Assisted Enzyme Engineering

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(2), P. 226 - 241

Published: Feb. 5, 2024

Enzymes can be engineered at the level of their amino acid sequences to optimize key properties such as expression, stability, substrate range, and catalytic efficiency-or even unlock new activities not found in nature. Because search space possible proteins is vast, enzyme engineering usually involves discovering an starting point that has some desired activity followed by directed evolution improve its "fitness" for a application. Recently, machine learning (ML) emerged powerful tool complement this empirical process. ML models contribute (1) discovery functional annotation known protein or generating novel with functions (2) navigating fitness landscapes optimization mappings between associated values. In Outlook, we explain how complements discuss future potential improved outcomes.

Language: Английский

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Direct visible-light-excited flavoproteins for redox-neutral asymmetric radical hydroarylation

Nature Catalysis, Journal Year: 2023, Volume and Issue: 6(11), P. 996 - 1004

Published: Sept. 14, 2023

Language: Английский

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Bioorthogonal Cu Single‐atom Nanozyme for Synergistic Nanocatalytic Therapy, Photothermal Therapy, Cuproptosis, and Immunotherapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(27)

Published: April 24, 2024

Single-atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in-depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis sputtered SAzymes by in situ bombarding-embedding technique. Using this method, copper (Cu) (CuSA) is developed unreported unique planar Cu-C

Language: Английский

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Boron catalysis in a designer enzyme

Nature, Journal Year: 2024, Volume and Issue: 629(8013), P. 824 - 829

Published: May 8, 2024

Language: Английский

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