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

Mengting Zhang,

Haidong Teng

и другие.

Bioresources and Bioprocessing, Год журнала: 2024, Номер 11(1)

Опубликована: Фев. 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

Язык: Английский

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

и другие.

Nature, Год журнала: 2024, Номер 629(8013), С. 824 - 829

Опубликована: Май 8, 2024

Язык: Английский

Процитировано

26
Noncanonical Amino Acids in Biocatalysis DOI Creative Commons
Zachary Birch-Price, Florence J. Hardy,

Thomas M. Lister

и другие.

Chemical Reviews, Год журнала: 2024, Номер 124(14), С. 8740 - 8786

Опубликована: Июль 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.

Язык: Английский

Процитировано

24
Cellular and Biophysical Applications of Genetic Code Expansion DOI
Han Yi, Seungeun Lee, Kyungdeok Seo

и другие.

Chemical Reviews, Год журнала: 2024, Номер 124(11), С. 7465 - 7530

Опубликована: Май 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.

Язык: Английский

Процитировано

13
A New Age of Biocatalysis Enabled by Generic Activation Modes DOI Creative Commons
Shubhanshu Jain, Felipe Ospina, Stephan C. Hammer

и другие.

JACS Au, Год журнала: 2024, Номер 4(6), С. 2068 - 2080

Опубликована: Май 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.

Язык: Английский

Процитировано

10
Iminium catalysis in natural Diels–Alderase DOI
Zuodong Sun,

Xin Zang,

Qingyang Zhou

и другие.

Nature Catalysis, Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Язык: Английский

Процитировано

2
The Transformative Power of Biocatalysis in Convergent Synthesis DOI
Lara Zetzsche, Suman Chakrabarty, Alison R. H. Narayan

и другие.

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(12), С. 5214 - 5225

Опубликована: Март 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.

Язык: Английский

Процитировано

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

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(30)

Опубликована: Май 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

Язык: Английский

Процитировано

31
Friedel–Crafts reactions for biomolecular chemistry DOI Creative Commons
Jun Ohata

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер 22(18), С. 3544 - 3558

Опубликована: Янв. 1, 2024

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

Язык: Английский

Процитировано

9
Light-Driven Deracemization by a Designed Photoenzyme DOI
Min Li, Yan Zhang, Kai Fu

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

The creation of enzymes with abiological abilities offers exciting opportunities to access new-to-nature biocatalysis beyond that found in nature. Here, we repurpose a novel protein scaffold, CTB10, as an artificial photoenzyme through genetic code expansion. It enables catalytic deracemization cyclopropane, process remains inaccessible traditional due its thermodynamically unfavorable Following structural optimization directed evolution, broad substrate scope high enantioselectivities is achieved. Furthermore, the crystal structure CTB10-based photoenzyme-substrate complex well demonstrates how chiral cavity sculpted promote efficient and selective light-enabled deracemization. Therefore, this study unlocks potential for achieving challenging biocatalysis.

Язык: Английский

Процитировано

1
Engineering enzyme activity using an expanded amino acid alphabet DOI Creative Commons
Zachary Birch-Price, Christopher J. Taylor, Mary Ortmayer

и другие.

Protein Engineering Design and Selection, Год журнала: 2022, Номер 36

Опубликована: Ноя. 10, 2022

Abstract Enzyme design and engineering strategies are typically constrained by the limited size of nature’s genetic alphabet, comprised only 20 canonical amino acids. In recent years, site-selective incorporation non-canonical acids (ncAAs) via an expanded code has emerged as a powerful means inserting new functional components into proteins, with hundreds structurally diverse ncAAs now available. Here, we highlight how emergence repertoire opened avenues in enzyme engineering. have been used to probe complex biological mechanisms, augment function and, most ambitiously, embed catalytic mechanisms protein active sites that would be challenging access within constraints code. We predict studies reviewed this article, along further advances expansion technology, will establish ncAA increasingly important tool for biocatalysis coming years.

Язык: Английский

Процитировано

28