Rationally introducing non-canonical amino acids to enhance catalytic activity of LmrR for Henry reaction DOI Creative Commons
Lan Wang,

Mengting Zhang,

Haidong Teng

et al.

Bioresources and Bioprocessing, Journal Year: 2024, Volume and Issue: 11(1)

Published: Feb. 29, 2024

Abstract The use of enzymes to catalyze Henry reaction has advantages mild conditions and low contamination, but enzyme activity promiscuous catalysis limits its application. Here, rational design was first performed identify the key amino acid residues in catalyzed by Lactococcal multidrug resistance Regulator (LmrR). Further, non-canonical acids were introduced into LmrR, successfully obtaining variants that enhanced catalytic LmrR. best variant, V15CNF, showed a 184% increase compared wild type, 1.92 times more effective than optimal natural V15F. Additionally, this variant had broad substrate spectrum, capable catalyzing reactions between various aromatic aldehydes nitromethane, with product yielded ranging from 55 99%. This study improved enzymatic enhancing affinity substrates, while breaking limited types introducing enzyme, providing strategies for molecular modifications. Graphical

Language: Английский

Boron catalysis in a designer enzyme DOI
Lars Longwitz, Reuben B. Leveson‐Gower, H.J. Rozeboom

et al.

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

Published: May 8, 2024

Language: Английский

Citations

25
Noncanonical Amino Acids in Biocatalysis DOI Creative Commons
Zachary Birch-Price, Florence J. Hardy,

Thomas M. Lister

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(14), P. 8740 - 8786

Published: July 3, 2024

In recent years, powerful genetic code reprogramming methods have emerged that allow new functional components to be embedded into proteins as noncanonical amino acid (ncAA) side chains. this review, we will illustrate how the availability of an expanded set building blocks has opened a wealth opportunities in enzymology and biocatalysis research. Genetic provided insights enzyme mechanisms by allowing introduction spectroscopic probes targeted replacement individual atoms or groups. NcAAs also been used develop engineered biocatalysts with improved activity, selectivity, stability, well enzymes artificial regulatory elements are responsive external stimuli. Perhaps most ambitiously, combination laboratory evolution given rise classes use ncAAs key catalytic elements. With framework for developing ncAA-containing now firmly established, optimistic become progressively more tool armory designers engineers coming years.

Language: Английский

Citations

22
Iminium catalysis in natural Diels–Alderase DOI
Zuodong Sun,

Xin Zang,

Qingyang Zhou

et al.

Nature Catalysis, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Language: Английский

Citations

2
Cellular and Biophysical Applications of Genetic Code Expansion DOI
Han Yi, Seungeun Lee, Kyungdeok Seo

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(11), P. 7465 - 7530

Published: May 16, 2024

Despite their diverse functions, proteins are inherently constructed from a limited set of building blocks. These compositional constraints pose significant challenges to protein research and its practical applications. Strategically manipulating the cellular synthesis system incorporate novel blocks has emerged as critical approach for overcoming these in application. In past two decades, field genetic code expansion (GCE) achieved advancements, enabling integration numerous functionalities into across variety organisms. This technological evolution paved way extensive application multiple domains, including imaging, introduction probes research, analysis protein–protein interactions, spatiotemporal control function, exploration proteome changes induced by external stimuli, endowed with functions. this comprehensive Review, we aim provide an overview biophysical applications that have employed GCE technology over decades.

Language: Английский

Citations

12
The Transformative Power of Biocatalysis in Convergent Synthesis DOI
Lara Zetzsche, Suman Chakrabarty, Alison R. H. Narayan

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(12), P. 5214 - 5225

Published: March 15, 2022

Achieving convergent synthetic strategies has long been a gold standard in constructing complex molecular skeletons, allowing for the rapid generation of complexity comparatively streamlined routes. Traditionally, biocatalysis not played prominent role laboratory synthesis, with application biocatalysts primarily limited to synthesis chiral fragments. Although use enzymes enable approaches is relatively new and emerging, combining efficiency transformations selectivity achievable through creates opportunities efficient strategies. This Perspective provides an overview recent developments biocatalytic offers insights into advantages these methods compared their small molecule-based counterparts.

Language: Английский

Citations

38
Unlocking New Reactivities in Enzymes by Iminium Catalysis DOI
Guangcai Xu, Gerrit J. Poelarends

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(30)

Published: May 7, 2022

Abstract The application of biocatalysis in conquering challenging synthesis requires the constant input new enzymes. Developing novel biocatalysts by absorbing catalysis modes from synthetic chemistry has yielded fruitful new‐to‐nature Organocatalysis was originally bio‐inspired and become third pillar asymmetric catalysis. Transferring organocatalytic reactions back to enzyme platforms is a promising approach for biocatalyst creation. Herein, we summarize recent developments design that adopt iminium catalysis, fundamental branch organocatalysis. By repurposing existing enzymes or constructing artificial enzymes, various have been created optimized via protein engineering promote valuable abiological transformations. Recent advances illustrate power combining chemomimetic directed evolution generate useful

Language: Английский

Citations

29
A New Age of Biocatalysis Enabled by Generic Activation Modes DOI Creative Commons
Shubhanshu Jain, Felipe Ospina, Stephan C. Hammer

et al.

JACS Au, Journal Year: 2024, Volume and Issue: 4(6), P. 2068 - 2080

Published: May 31, 2024

Biocatalysis is currently undergoing a profound transformation. The field moves from relying on nature's chemical logic to discipline that exploits generic activation modes, allowing for novel biocatalytic reactions and, in many instances, entirely new chemistry. Generic modes enable wide range of reaction types and played pivotal role advancing the fields organo- photocatalysis. This perspective aims summarize principal harnessed enzymes develop biocatalysts. Although extensively researched past, highlighted when applied within enzyme active sites, facilitate transformations have largely eluded efficient selective catalysis. advance attributed multiple tunable interactions substrate binding pocket precisely control competing pathways transition states. We will highlight cases synthetic methodologies achieved by engineered provide insights into potential future developments this rapidly evolving field.

Language: Английский

Citations

8
Secondary Amine Catalysis in Enzyme Design: Broadening Protein Template Diversity through Genetic Code Expansion DOI Creative Commons
Thomas L. Williams, Irshad Maajid Taily,

Lewis Hatton

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 28, 2024

Abstract Secondary amines, due to their reactivity, can transform protein templates into catalytically active entities, accelerating the development of artificial enzymes. However, existing methods, predominantly reliant on modified ligands or N‐terminal prolines, impose significant limitations template selection. In this study, genetic code expansion was used break boundary, enabling secondary amines be incorporated alternative proteins and positions choice. Pyrrolysine analogues carrying different could superfolder green fluorescent (sfGFP), multidrug‐binding LmrR nucleotide‐binding dihydrofolate reductase (DHFR). Notably, analogue containing a D‐proline moiety demonstrated both proteolytic stability catalytic activity, conferring DHFR with desired transfer hydrogenation activity. While variants were confined biomimetic 1‐benzyl‐1,4‐dihydronicotinamide (BNAH) as hydride source, optimal variant favorably pro‐ R from NADPH for stereoselective reactions ( e.r . up 92 : 8), highlighting that switch broaden nucleophile option catalysis. Owing cofactor compatibility, DHFR‐based amine catalysis integrated an enzymatic recycling scheme. This established method shows substantial potential in enzyme design, applicable studies evolution new biocatalysts.

Language: Английский

Citations

6
Friedel–Crafts reactions for biomolecular chemistry DOI Creative Commons
Jun Ohata

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(18), P. 3544 - 3558

Published: Jan. 1, 2024

This review demonstrates advances in Friedel–Crafts alkylation and acylation reactions a variety of biomolecular chemistry fields.

Language: Английский

Citations

6
Review on Recent Developments in Biocatalysts for Friedel–Crafts Reactions DOI
Vajinder Kumar, W. Bruce Turnbull, Avneesh Kumar

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(17), P. 10742 - 10763

Published: Aug. 17, 2022

The Friedel–Crafts (F–C) reaction has been a fundamental pillar of both academic and industrial synthetic organic chemistry since its discovery in 1873. Its success is based on the versatility applicability F–C reactions for wide range substrates, there have an impressive number publications patents describing catalytic methods. asymmetric version was discovered about 100 years after seminal work by Friedel Crafts become major area research. While chemical methods with much-improved efficacies scopes discovered, still suffer from limitations. Biocatalysis potential to be best solution this challenge because excellent selectivity (enantio-, chemo-, regioselectivity) displayed enzymes. In last two decades, advancements molecular biology techniques, bioinformatics, high-throughput screening, directed evolution, process scale-up led biocatalysis becoming mature field. It therefore not surprising that researchers around globe developed several biocatalysts reactions. Herein, we review recent developments design use stereoselective strategies performing

Language: Английский

Citations

27