Biocatalytic enantioselective formation and ring-opening of oxetanes DOI Creative Commons
Xia Hua, Yuanfei Wang, Xiao Jin

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 30, 2025

Although biocatalysis offers complementary or alternative approaches to traditional synthetic methods, the limited range of available enzymatic reactions currently poses challenges in synthesizing a diverse array desired compounds. Consequently, there is significant demand for developing novel biocatalytic processes enable that were previously unattainable. Herein, we report discovery and subsequent protein engineering unique halohydrin dehalogenase develop platform enantioselective formation ring-opening oxetanes. This platform, exhibiting high efficiency, excellent enantioselectivity, broad scopes, facilitates preparative-scale synthesis chiral oxetanes variety γ-substituted alcohols. Additionally, both oxetane are proven scalable large-scale transformations at substrate concentrations, can be integrated efficiently one-pot, one-catalyst cascade system. work expands toolbox non-natural will promote further exploration catalytic repertoire dehalogenases pharmaceutical chemistry. Oxetane four-membered, oxygen-containing heterocyclic compound importance medicinal chemistry drug development. Here, authors dehalogenase,

Language: Английский

Macrocyclization and Backbone Rearrangement During RiPP Biosynthesis by a SAM-Dependent Domain-of-Unknown-Function 692 DOI Creative Commons
Richard S. Ayikpoe, Lingyang Zhu, Jeff Y. Chen

et al.

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(5), P. 1008 - 1018

Published: April 24, 2023

The domain of unknown function 692 (DUF692) is an emerging family post-translational modification enzymes involved in the biosynthesis ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. Members this are multinuclear iron-containing enzymes, only two members have been functionally characterized to date: MbnB TglH. Here, we used bioinformatics select another member DUF692 family, ChrH, that encoded genomes Chryseobacterium genus along with a partner protein ChrI. We structurally ChrH reaction product show enzyme complex catalyzes unprecedented chemical transformation results formation macrocycle, imidazolidinedione heterocycle, thioaminals, thiomethyl group. Based on isotopic labeling studies, propose mechanism for four-electron oxidation methylation substrate peptide. This work identifies first SAM-dependent catalyzed by complex, further expanding repertoire remarkable reactions these enzymes. three currently members, suggest be called non-heme iron dependent oxidative (MNIOs).

Language: Английский

Citations

35
Engineering ketoreductases for the enantioselective synthesis of chiral alcohols DOI Creative Commons
Qiao Li,

Zhiyuan Luo,

Haomin Chen

et al.

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(49), P. 7518 - 7533

Published: Jan. 1, 2023

This review summarises the use of engineered ketoreductases (KREDS), both as whole microbial cells and isolated enzymes, in highly enantiospecific reduction prochiral ketones.

Language: Английский

Citations

29
Spatial Localization of Two Enzymes at Pickering Emulsion Droplet Interfaces for Cascade Reactions DOI
Ke Li, Houbing Zou, Rammile Ettelaie

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 15, 2023

Developing biocatalytic cascades in abiological conditions is of utmost significance, but such processes often suffer from low reaction efficiency because incompatible environments and suppressed intermediate transportation. Herein we report a new type cascade by localizing two different enzymes separately the outer inner interfacial layers Pickering emulsion droplets. This versatile approach enables localization their preferred microenvironments simultaneously nanoscale proximity each other. The thus-designed show outstanding catalytic alkene epoxidation thioether oxidation with situ generation hydrogen peroxide under mild conditions, 6.9-13.6 times higher than free solution multi-enzymatic counterparts. remarkable effect droplets was found to be responsible for significantly enhanced cascading efficiency.

Language: Английский

Citations

28
Application of Immobilized Enzymes in Flow Biocatalysis for Efficient Synthesis DOI
Zhongyao Tang, Yuri Oku, Tomoko Matsuda

et al.

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(5), P. 1308 - 1326

Published: March 8, 2024

Flow chemistry as well biocatalysis contribute to achieve green industries and sustainable development. Now there is an approach that combines them, called flow biocatalysis, which attracts more attention. In enzyme immobilization plays a powerful role in promoting its This review begins with general introduction of then provides update on the application immobilized enzymes biocatalysis. Oxidation–reduction, hydrolysis–esterification, transferase reaction, condensation, carboxylation, multistep cascade reactions continuous-flow process are discussed detail.

Language: Английский

Citations

15
Co-immobilization of whole cells and enzymes by covalent organic framework for biocatalysis process intensification DOI Creative Commons

D. Zheng,

Yunlong Zheng,

Jun‐Jie Tan

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 29, 2024

Abstract Co-immobilization of cells and enzymes is often essential for the cascade biocatalytic processes industrial-scale feasibility but remains a vast challenge. Herein, we create facile co-immobilization platform integrating in covalent organic frameworks (COFs) to realize highly efficient inulinase E. coli bioconversion natural products. Enzymes can be uniformly immobilized COF armor, which coats on cell surface produce biocatalysts with high efficiency, stability recyclability. Furthermore, this one-pot situ synthesis process facilitates gram-scale fabrication enzyme-cell biocatalysts, generate continuous-flow device conversing inulin D-allulose, achieving space-time yield 161.28 g L −1 d (remaining >90% initial catalytic efficiency after 7 days continuous reaction). The created applied various (e.g., , Yeast) enzymes, demonstrating excellent universality. This study paves pathway break bottleneck extra- intracellular catalysis, creates high-performance customizable biomanufacturing, expands scope biocatalysis intensification.

Language: Английский

Citations

15
Genome Mining for New Enzyme Chemistry DOI Creative Commons
Dinh Thanh Nguyen, Douglas A. Mitchell, Wilfred A. van der Donk

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(7), P. 4536 - 4553

Published: March 12, 2024

A revolution in the field of biocatalysis has enabled scalable access to compounds high societal values using enzymes. The construction biocatalytic routes relies on reservoir available enzymatic transformations. review uncharacterized proteins predicted from genomic sequencing projects shows that a treasure trove enzyme chemistry awaits be uncovered. This Review highlights transformations discovered through various genome mining methods and showcases their potential future applications biocatalysis.

Language: Английский

Citations

14
Biosynthesis of Macrocyclic Peptides with C-Terminal β-Amino-α-keto Acid Groups by Three Different Metalloenzymes DOI Creative Commons
Dinh Thanh Nguyen, Lingyang Zhu, Danielle L. Gray

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(5), P. 1022 - 1032

Published: April 11, 2024

Advances in genome sequencing and bioinformatics methods have identified a myriad of biosynthetic gene clusters (BGCs) encoding uncharacterized molecules. By mining genomes for BGCs containing prevalent peptide-binding domain used the biosynthesis ribosomally synthesized post-translationally modified peptides (RiPPs), we uncovered new compound class involving modifications installed by cytochrome P450, multinuclear iron-dependent non-heme oxidative enzyme (MNIO, formerly DUF692), cobalamin- radical

Language: Английский

Citations

13
Advances in cofactor immobilization for enhanced continuous-flow biocatalysis DOI Creative Commons
Bente Reus, Matteo Damian, Francesco G. Mutti

et al.

Journal of Flow Chemistry, Journal Year: 2024, Volume and Issue: 14(1), P. 219 - 238

Published: Feb. 14, 2024

Abstract The merging of biocatalysis with continuous-flow chemistry opens up new opportunities for sustainable and efficient chemical synthesis. Cofactor-dependent enzymes are essential various industrially attractive biocatalytic reactions. However, implementing these reactions in industry remains challenging due to the inherent cost cofactors requirement their external supply significant quantities. development efficient, low cost, simple versatile methods cofactor immobilization can address this important obstacle flow. This review explores recent progress by analyzing advantages current limitations available that comprise covalent tethering, ionic adsorption, physical entrapment, hybrid variations thereof. Moreover, analyzes all techniques specifically utilization provides a perspective future work area. will serve as guide steering field towards more economically viable biocatalysis. Graphical

Language: Английский

Citations

12
Precision Engineering of the Co‐immobilization of Enzymes for Cascade Biocatalysis DOI

Zhiyuan Luo,

Li Qiao, Haomin Chen

et al.

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

Published: April 1, 2024

Abstract The design and orderly layered co‐immobilization of multiple enzymes on resin particles remain challenging. In this study, the SpyTag/SpyCatcher binding pair was fused to N‐terminus an alcohol dehydrogenase (ADH) aldo‐keto reductase (AKR), respectively. A non‐canonical amino acid (ncAA), p ‐azido‐L‐phenylalanine (p‐AzF), as anchor for covalent bonding enzymes, genetically inserted into preselected sites in AKR ADH. Employing two bioorthogonal counterparts azide–alkyne cycloaddition immobilization ADH enabled sequential dual‐enzyme coating porous microspheres. ordered reactor subsequently used synthesize ( S )‐1‐(2‐chlorophenyl)ethanol asymmetrically from corresponding prochiral ketone, enabling situ regeneration NADPH. exhibited a high catalytic conversion 74 % good reproducibility, retaining 80 its initial activity after six cycles. product had 99.9 ee, which that maintained each cycle. Additionally, double‐layer method significantly increased enzyme loading capacity, approximately 1.7 times greater than traditional single‐layer immobilization. More importantly, it simultaneously both purification carriers, thus providing convenient approach facilitate cascade biocatalysis.

Language: Английский

Citations

12
Immobilized Multi‐Enzyme/Nanozyme Biomimetic Cascade Catalysis for Biosensing Applications DOI
Xiaoli Cai,

Yuteng Huang,

Chengzhou Zhu

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Multiple enzyme-induced cascade catalysis has an indispensable role in the process of complex life activities, and is widely used to construct robust biosensors for analyzing various targets. The immobilized multi-enzyme system a novel biomimetic strategy that immobilizes enzymes with different functions stable carriers simulate synergistic multiple biological systems, which enables high stability efficiency enzymatic catalysis. Nanozymes, type nanomaterial intrinsic enzyme-like characteristics excellent stabilities, are also applied instead achieving better catalytic performance reaction stability. Due good stability, reusability, remarkably efficiency, multi-enzyme/nanozyme systems show distinct advantages promoting signal transduction amplification, thereby attracting vast research interest biosensing applications. This review focuses on progress recent years. construction approaches, factors affecting applications sensitive discussed detail. Further, their challenges outlooks future study provided.

Language: Английский

Citations

12