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.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 30, 2023

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 class involving modifications installed by cytochrome P450, multi-nuclear iron-dependent non-heme oxidative enzyme (MNIO, formerly DUF692), cobalamin- radical

Language: Английский

The E factor at 30: a passion for pollution prevention DOI Creative Commons
Roger A. Sheldon

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(5), P. 1704 - 1728

Published: Jan. 1, 2023

Publication of the E Factor drew attention to problem waste in chemicals manufacture. Thirty yeas later it is abundantly clear that underlying cause global environmental problems, from climate change plastic pollution.

Language: Английский

Citations

147
Multienzyme cascade for synthesis of hydroxytyrosol via engineered Escherichia coli DOI Creative Commons
Tianzhen Xiong, Xinmeng Li, Wei Liu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Language: Английский

Citations

2
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
Engineered repeat proteins as scaffolds to assemble multi-enzyme systems for efficient cell-free biosynthesis DOI Creative Commons
Alba Ledesma‐Fernandez, Susana Velasco‐Lozano, Javier Santiago‐Arcos

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 4, 2023

Multi-enzymatic cascades with enzymes arranged in close-proximity through a protein scaffold can trigger substrate channeling effect, allowing for efficient cofactor reuse industrial potential. However, precise nanometric organization of challenges the design scaffolds. In this study, we create nanometrically organized multi-enzymatic system exploiting engineered Tetrapeptide Repeat Affinity Proteins (TRAPs) as scaffolding biocatalysis. We genetically fuse TRAP domains and program them to selectively orthogonally recognize peptide-tags fused enzymes, which upon binding form spatially metabolomes. addition, encodes sites reversibly sequester reaction intermediates like cofactors via electrostatic interactions, increasing their local concentration and, consequently, catalytic efficiency. This concept is demonstrated biosynthesis amino acids amines using up three enzymes. Scaffolded multi-enzyme systems present 5-fold higher specific productivity than non-scaffolded ones. In-depth analysis suggests that NADH between assembled enhances overall cascade throughput product yield. Moreover, immobilize biomolecular on solid supports, creating reusable heterogeneous multi-functional biocatalysts consecutive operational batch cycles. Our results demonstrate potential TRAP-scaffolding spatial-organizing tools increase efficiency cell-free biosynthetic pathways.

Language: Английский

Citations

34
Building Enzymes through Design and Evolution DOI Creative Commons
Euan J. Hossack, Florence J. Hardy, Anthony P. Green

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(19), P. 12436 - 12444

Published: Sept. 7, 2023

Designing efficient enzymes is a formidable challenge at the forefront of modern biocatalysis. Here, we review recent developments in field and illustrate how interplay between computational design advanced protein engineering has given rise to with diverse activities. Natural proteins have been re-engineered computationally embed designed catalytic sites, affording active catalysts that can be optimized through laboratory evolution enhance efficiency selectivity. Computational tools reliably generate stable de novo shapes backbone geometries beyond those found nature, which serve as idealized templates for hosting sites. Genetic code reprogramming methods used introduce additional functional elements into sites expand range chemistries accessible designer enzymes. Finally, emergence powerful based on deep learning promises transformative impact by greatly increasing speed model accuracy. By bringing together latest experimental enzyme design, are optimistic ambition building useful biocatalysts from scratch within reach.

Language: Английский

Citations

31
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
Green chemistry and biocatalysis: Engineering a sustainable future DOI
Roger A. Sheldon

Catalysis Today, Journal Year: 2024, Volume and Issue: 431, P. 114571 - 114571

Published: Feb. 17, 2024

Language: Английский

Citations

13
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
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

12
Opportunities and Challenges of Metal–Organic Framework Micro/Nano Reactors for Cascade Reactions DOI Creative Commons
Peng Wu, Yanhua Zhao, Xinglong Zhang

et al.

JACS Au, Journal Year: 2023, Volume and Issue: 3(9), P. 2413 - 2435

Published: Aug. 30, 2023

Building bridges among different types of catalysts to construct cascades is a highly worthwhile pursuit, such as chemo-, bio-, and chemo-bio cascade reactions. Cascade reactions can improve the reaction efficiency selectivity while reducing steps separation purification, thereby promoting development "green chemistry". However, compatibility issues in pose significant constraints on this field, particularly concerning diverse catalyst types, conditions, rates. Metal-organic framework micro/nano reactors (MOF-MNRs) are porous crystalline materials formed by self-assembly coordination metal sites organic ligands, possessing periodic network structure. Due uniform pore size with capability controlling selective transfer substances well protecting active organic-inorganic parts providing reactive microenvironment, MOF-MNRs have attracted attention recent years. In Perspective, we first discuss how address using MOF-MNRs, including structural design synthetic strategies. Then summarize research progress various Finally, analyze challenges facing potential breakthrough directions opportunities for future.

Language: Английский

Citations

14