Biocatalysis for the Synthesis of Active Pharmaceutical Ingredients in Deep Eutectic Solvents: State-of-the-Art and Prospects

Catalysts, Journal Year: 2024, Volume and Issue: 14(1), P. 84 - 84

Published: Jan. 19, 2024

Biocatalysis holds immense potential for pharmaceutical development as it enables synthetic routes to various chiral building blocks with unparalleled selectivity. Therein, solvent and water use account a large contribution the environmental impact of reactions. In spirit Green Chemistry, transition from traditional highly diluted aqueous systems intensified non-aqueous media overcome limitations (e.g., shortages, recalcitrant wastewater treatments, low substrate loadings) has been observed. Benefiting spectacular advances in enzyme stabilization techniques, plethora biotransformations non-conventional have established. Deep eutectic solvents (DESs) emerge sort (potentially) greener medium increasing biocatalysis. This review discusses state-of-the-art DESs focus on biocatalytic pathways synthesis active ingredients (APIs). Representative examples different classes are discussed, together critical vision discussing prospects using

Language: Английский

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Enabling Broader Adoption of Biocatalysis in Organic Chemistry

JACS Au, Journal Year: 2023, Volume and Issue: 3(8), P. 2073 - 2085

Published: July 19, 2023

Biocatalysis is becoming an increasingly impactful method in contemporary synthetic chemistry for target molecule synthesis. The selectivity imparted by enzymes has been leveraged to complete previously intractable chemical transformations and improve routes toward complex molecules. However, the implementation of biocatalysis mainstream organic gradual this point. This partly due a set historical technological barriers that have prevented chemists from using as tool with utility parallels alternative modes catalysis. In Perspective, we discuss these how they hindered adoption enzyme catalysts into strategies. We also summarize tools resources already enable use biocatalysts. Furthermore, ways further lower broader community through dissemination resources, demystifying biocatalytic reactions, increasing collaboration across field.

Language: Английский

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Non-Native Site-Selective Enzyme Catalysis

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(16), P. 10381 - 10431

Published: July 31, 2023

The ability to site-selectively modify equivalent functional groups in a molecule has the potential streamline syntheses and increase product yields by lowering step counts. Enzymes catalyze site-selective transformations throughout primary secondary metabolism, but leveraging this capability for non-native substrates reactions requires detailed understanding of limitations enzyme catalysis how these bounds can be extended protein engineering. In review, we discuss representative examples involving group manipulation C-H bond functionalization. We include illustrative native catalysis, our focus is on cases often using engineered enzymes. then use enzymes chemoenzymatic target-oriented synthesis conclude with survey tools techniques that could expand scope catalysis.

Language: Английский

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Practical Machine Learning-Assisted Design Protocol for Protein Engineering: Transaminase Engineering for the Conversion of Bulky Substrates

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6462 - 6469

Published: April 12, 2024

Protein engineering is essential for improving the catalytic performance of enzymes applications in biocatalysis, which machine learning provides an emerging approach variant design. Transaminases are powerful biocatalysts stereoselective synthesis chiral amines but one major challenge their limited substrate scope. We present a general and practical design protocol protein to combine advantages three strategies, including directed evolution, rational design, learning, demonstrate application transaminases with higher activity toward bulky substrates. A high-quality data set was obtained by selected key positions, then applied create model transaminase activity. This data-assisted optimized variants, showed improved (up 3-fold over parent) substrates, maintaining enantioselectivity starting enzyme scaffold as well enantiomeric excess >99%ee).

Language: Английский

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Advances in cofactor immobilization for enhanced continuous-flow biocatalysis

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

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Low-energy photoredox catalysis

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Language: Английский

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Enzymatic Stereodivergent Access to Fluorinated β-Lactam Pharmacophores via Triple-Parameter Engineered Ketoreductases

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(8), P. 6358 - 6368

Published: April 11, 2024

Enzyme-catalyzed stereodivergent synthesis to access all possible stereoisomers of organofluorine compounds bearing multiple stereogenic centers remains an important and challenging subject. By integrative data-driven mining mechanism-guided engineering ketoreductases, we identified a biocatalytic platform produce four stereoisomeric fluoroalkyl amino acid esters two vicinal stereocenters. Fast triple-parameter coevolution via semirational CAST/ISM strategy provided the quadruple mutant M5 (A140K/L203T/G92A/V84I) ketoreductase BgADH not only displayed high stereoselectivity toward target (99:1 dr, 99% ee) but also observed with enhanced activity (kcat/Km, 6.3 folds) improved thermostability (T5015, 4 °C). Crystal structural analysis molecular dynamics (MD) simulation studies unveil residues (A140 F148) be key sites that are responsible for control stereoselectivity. The L203T/G92A mutation by affecting conformational distribution α-helix within active-site region, V84I thermal stability strengthening hydrogen bonding network neighboring residues. synthetic utility was further demonstrated substrate scope expansion, gram-scale reactions (648 g L–1 day–1), transformations chiral fluorinated β-lactams antibiotic carbapenem cores.

Language: Английский

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Enhancing Lipase Immobilization via Physical Adsorption: Advancements in Stability, Reusability, and Industrial Applications for Sustainable Biotechnological Processes

ACS Omega, Journal Year: 2024, Volume and Issue: 9(47), P. 46698 - 46732

Published: Nov. 14, 2024

Immobilization of lipases by physical adsorption improves their stability, recovery, and reusability in biotechnological processes. The present review provides an advanced bibliometric analysis a comprehensive overview research progress this field. By searching Web Science, 39,575 publications were analyzed, 325 relevant articles selected. Key journals, countries, institutions, authors identified. most cited focus on biofuel production industrial applications. revealed four themes with the biofuel. method is effective when appropriate support used. Despite decrease patent applications, interest remains high. Future studies should optimizing materials exploring new applications technique. detailed understanding immobilization adsorption.

Language: Английский

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Protein Recognition Methods for Diagnostics and Therapy

BBA Advances, Journal Year: 2025, Volume and Issue: 7, P. 100149 - 100149

Published: Jan. 1, 2025

The fundamental biological processes involving highly specific interactions between proteins and other motifs are the pillars of protein recognition mechanisms. These crucial for systems, often having significant implications within diagnostics therapy development. Protein specificity reliant on structural compatibility, dynamic conformational changes, biochemical interactions-all which grounded in molecular forces like hydrogen bonding, ionic interactions, van der Waals forces. Advanced characterization tools have improved our understanding revealing kinetics thermodynamics these In parallel, new computing methods, including artificial intelligence, docking, dynamical simulations, increased prediction accuracy leading to well-defined interaction sites binding information. is pivotal diagnostic methods ELISAs biosensors, disease detection applications. therapeutics, plays an important role drug development, enabling design small molecules, peptides, monoclonal antibodies. Despite recent progress, there many challenges remaining fully understand recognition, particularly complex cell environment. require future work studies enhance therapeutic researchers using screening identify, assess, optimize clinical translation.

Language: Английский

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Unraveling the molecular basis of substrate specificity and halogen activation in vanadium-dependent haloperoxidases

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

Published: Feb. 28, 2025

Abstract Vanadium-dependent haloperoxidases (VHPOs) are biotechnologically valuable and operationally versatile biocatalysts. VHPOs share remarkable active-site structural similarities yet display variable reactivity selectivity. The factors dictating substrate specificity and, thus, a general understanding of VHPO reaction control still need to be discovered. This work’s strategic single-point mutation in the cyanobacterial bromoperoxidase Am facilitates selectivity switch allow aryl chlorination. induces loop formation that interacts with neighboring protein monomer, creating tunnel active sites. Structural analysis substrate-R425S-mutant complex reveals substrate-binding site at interface two adjacent units. There, residues Glu139 Phe401 interact arenes, extending residence time close vanadate cofactor stabilizing intermediates. Our findings validate long-debated existence direct binding provide detailed mechanistic understanding. work will pave way for broader application diverse chemical processes.

Language: Английский

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