Enzymatic Strategies for the Biosynthesis of N‐Acyl Amino Acid Amides DOI
Glen Kai Bin Kua,

Giang K. T. Nguyen,

Zhi Li

et al.

ChemBioChem, Journal Year: 2023, Volume and Issue: 25(4)

Published: Dec. 5, 2023

Abstract Amide bond‐containing biomolecules are functionally significant and useful compounds with diverse applications. For example, N‐acyl amino acids (NAAAs) an important class of lipoamino acid amides extensive use in food, cosmetic pharmaceutical industries. Their conventional chemical synthesis involves the toxic chlorinating agents for carboxylic activation. Enzyme‐catalyzed biotransformation green these is therefore highly desirable. Here, we review a range enzymes suitable NAAA their strategies adopted Generally, ATP‐dependent biosynthesis acyl‐adenylating that couple hydrolysis phosphoanhydride bond ATP formation acyl‐adenylate intermediate. In contrast, ATP‐independent involve hydrolases such as lipases or aminoacylases, which rely on transient activation acid. This occurs either through acyl‐enzyme intermediate by favorable interactions surrounding residues to anchor acyl donor orientation incoming amine nucleophile. Recently, development alternative pathway involving ester‐amide interconversion has unraveled another possible strategy amide esterification‐aminolysis cascade reactions, potentially expanding substrate scope catalyze amides.

Language: Английский

Contemporary Approaches for Amide Bond Formation DOI
Paola Acosta‐Guzmán, Andrea Ojeda‐Porras, Diego Gamba‐Sánchez

et al.

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4359 - 4391

Published: Nov. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Language: Английский

Citations

51
Accelerated enzyme engineering by machine-learning guided cell-free expression DOI Creative Commons
Grant M. Landwehr, Jonathan W. Bogart,

Carol Magalhaes

et al.

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

Published: Jan. 20, 2025

Language: Английский

Citations

12
Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors DOI Creative Commons
Mengting Liu,

Xin Zang,

Niko Vlahakis

et al.

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Abstract E-64 is an irreversible cysteine protease inhibitor prominently used in chemical biology and drug discovery. Here we uncover a nonribosomal peptide synthetase-independent biosynthetic pathway for E-64, which widely conserved fungi. The starts with epoxidation of fumaric acid to the warhead (2 S ,3 )- trans -epoxysuccinic Fe(II)/α-ketoglutarate-dependent oxygenase, followed by successive condensation l -amino adenosine triphosphate grasp enzyme amine fungal example amide bond synthetase. Both bond-forming enzymes display notable biocatalytic potential, including scalability, stereoselectivity toward broader substrate scopes forming bonds. Biocatalytic cascade these generated library inhibitors, leading more potent cathepsin inhibitors. Additionally, one-pot reactions enabled preparative synthesis clinically relevant Our work highlights importance investigation discovery potential synthesizing small-molecule libraries.

Language: Английский

Citations

2
RetroBioCat Database: A Platform for Collaborative Curation and Automated Meta-Analysis of Biocatalysis Data DOI Creative Commons
William Finnigan, Max Lubberink, Lorna J. Hepworth

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(17), P. 11771 - 11780

Published: Aug. 22, 2023

Despite the increasing use of biocatalysis for organic synthesis, there are currently no databases that adequately capture synthetic biotransformations. The lack a database prevents accelerating biocatalyst characterization efforts from being leveraged to quickly identify candidate enzymes reactions or cascades, slowing their development. RetroBioCat Database (available at retrobiocat.com) addresses this gap by capturing information on biotransformations and providing an analysis platform allows data be searched explored through range highly interactive visualization tools. This makes it simple explore available enzymes, substrate scopes, how characterized related each other wider sequence space. Data entry is facilitated openly accessible curation platform, featuring automated tools accelerate process. democratizes knowledge has potential biocatalytic reaction development, making valuable resource community.

Language: Английский

Citations

18
N‐Carboxyanhydrides (NCAs): Unorthodox and Useful Reagents for Amide Synthesis DOI Creative Commons
Simon N. Smith, Stephen J. Connon

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 19, 2024

Abstract N‐ Carboxyanhydrides (NCAs) are compounds derived from the addition of a carboxylic acid to an isocyanate, and known form amides readily with release CO 2 as by‐product. NCAs have been for over 120 years, but despite their lengthy history, remained so far overshadowed by more traditional approaches amide bond formation. In this review, potential utility in context formation is reviewed preparation, reactivity practical application also discussed.

Language: Английский

Citations

8
Biocatalytic Heteroaromatic Amide Formation in Water Enabled by a Catalytic Tetrad and Two Access Tunnels DOI Creative Commons

Erna Zukić,

Daniel Mokos,

M. WEBER

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 8913 - 8921

Published: May 25, 2024

The amide moiety belongs to the most common motives in pharmaceutical chemistry, present many prescribed small-molecule pharmaceuticals. Methods for its manufacture are still high demand, especially using water/buffer as a solvent and avoiding stoichiometric amounts of activation reagents. Herein, we identified from library lipases/esterases/acyltransferases variants thereof lipase originating Sphingomonas sp. HXN-200 (SpL) able form amides aqueous solution starting broad scope sterically demanding heteroaromatic ethyl esters well aliphatic amines, reaching isolated yields up 99% on preparative scale space time 864 g L–1 d–1; thus, selected cases, was formed within minutes. enzyme features an aspartate next canonical serine catalytic triad, which essential formation. Furthermore, structure revealed two tunnels active site, presumably one ester amine, permit bringing together amine site. This work shows that biocatalytic formation various five- six-membered buffer can serve platform synthesis.

Language: Английский

Citations

8
Condensation of carboxylic acids with amines using the Boc2O/DMAP system under solvent-free conditions DOI
Mourad Boukachabia, Mounia Merabet‐Khelassi, Olivier Riant

et al.

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We have developed an efficient solvent-free protocol for amide bond formation using Boc 2 O/DMAP, involving the in situ generation of a mixed anhydride and proceeding via sequential mechanism.

Language: Английский

Citations

1
Broad Spectrum Enantioselective Amide Bond Synthetase from Streptoalloteichus hindustanus DOI Creative Commons
Qingyun Tang, Mark Petchey, Benjamin Rowlinson

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(2), P. 1021 - 1029

Published: Jan. 6, 2024

The synthesis of amide bonds is one the most frequently performed reactions in pharmaceutical synthesis, but requirement for stoichiometric quantities coupling agents and activated substrates established methods has prompted interest biocatalytic alternatives. Amide Bond Synthetases (ABSs) actively catalyze both ATP-dependent adenylation carboxylic acid their subsequent amidation using an amine nucleophile, within active site enzyme, enabling use only a small excess partner. We have assessed ability ABS from

Language: Английский

Citations

6
Recent Progress on Green Methods and Technologies for Efficient Formation of Amide Bonds DOI Open Access
Jing Huang, Yihua Yang, Zhan‐Hui Zhang

et al.

Chinese Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 44(2), P. 409 - 409

Published: Jan. 1, 2024

Amide bond constructions are crucial in peptide synthesis and pharmaceutical chemistry research.The traditional methods of require the use excessive amounts reagents solvents, posing a threat to environment human health.It is still current research focus develop environmentally friendly novel acylation efficient, green, sustainable amide methods.From green chemistry's principles, this paper focused on efficient formation bonds peptide, including catalysis elemental organic chemicals, some solvents reagents, physical strengthening methods, etc.The application these technologies was also discussed chemistry.

Language: Английский

Citations

6
Waste Valorization in a Sustainable Bio‐Based Economy: The Road to Carbon Neutrality DOI Creative Commons
Roger A. Sheldon

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract The development of sustainable chemistry underlying the quest to minimize and/or valorize waste in carbon‐neutral manufacture chemicals is followed over last four five decades. Both chemo‐ and biocatalysis have played an indispensable role this odyssey. particular developments protein engineering, metagenomics bioinformatics preceding three decades a crucial supporting facilitating widespread application both whole cell cell‐free biocatalysis. pressing need, driven by climate change mitigation, for drastic reduction greenhouse gas (GHG) emissions, has precipitated energy transition based on decarbonization defossilization organic production. latter involves biomass CO 2 as feedstock green electricity generated using solar, wind, hydroelectric or nuclear energy. use polysaccharides feedstocks will underpin renaissance carbohydrate with pentoses hexoses base bio‐based solvents polymers environmentally friendly downstream products. availability inexpensive solar led increasing attention electro(bio)catalysis photo(bio)catalysis which turn leading myriad innovations these fields.

Language: Английский

Citations

6