The Quantum Chemical Cluster Approach in Biocatalysis

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(8), P. 938 - 947

Published: March 28, 2023

The quantum chemical cluster approach has been used for modeling enzyme active sites and reaction mechanisms more than two decades. In this methodology, a relatively small part of the around site is selected as model, methods, typically density functional theory, are to calculate energies other properties. surrounding modeled using implicit solvation atom fixing techniques. Over years, large number have solved method. models gradually become larger result faster computers, new kinds questions addressed. Account, we review how can be utilized in field biocatalysis. Examples from our recent work chosen illustrate various aspects methodology. use model explore substrate binding discussed first. It emphasized that comprehensive search necessary order identify lowest-energy mode(s). also argued best mode might not productive one, full reactions enzyme-substrate complexes therefore considered find pathway. Next, examples given help elucidation detailed biocatalytically interesting enzymes, knowledge exploited develop enzymes with functions or understand reasons lack activity toward non-natural substrates. context phenolic acid decarboxylase metal-dependent decarboxylases amidohydrolase superfamily. application investigation enzymatic enantioselectivity discussed. strictosidine synthase case study, where calculations could reproduce rationalize selectivities both natural Finally, discuss guide rational design variants improved selectivity. Acyl transferase Mycobacterium smegmatis serves an instructive example here, which pinpoint factors controlling specificity enantioselectivity. cases Account highlight thus value tool complements experiments computational techniques provides insights existing tailored

Language: Английский

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The Transformative Power of Biocatalysis in Convergent Synthesis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(12), P. 5214 - 5225

Published: March 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.

Language: Английский

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A robust heterogeneous chiral phosphoric acid enables multi decagram scale production of optically active N,S-ketals

Green Chemistry, Journal Year: 2024, Volume and Issue: 26(8), P. 4593 - 4599

Published: Jan. 1, 2024

A multi-decagram scale synthesis of enantioenriched N,S -ketals was achieved by using a robust heterogeneous organocatalyst. new reactor design crucial to enable the scaling up this reaction while overall catalyst loading below 0.1%.

Language: Английский

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One-Pot Sequential Two-Step Photo-Biocatalytic Deracemization of sec-Alcohols Combining Photocatalytic Oxidation and Bioreduction

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(3), P. 1808 - 1823

Published: Jan. 19, 2024

Chiral alcohols are versatile building blocks and of particular interest in the asymmetric synthesis nonracemic active pharmaceutical ingredients, agrochemicals, fragrances, flavors, natural products, etc. Herein, we report on a "one-pot sequential two-step" concurrent oxidation–reduction photobiocatalytic process to synthesize enantiomerically enriched alcohols. In this regard, an efficient photocatalytic system based irradiation with 440 nm blue LEDs presence 9-fluorenone as metal-free photocatalyst molecular oxygen terminal oxidant dry DMSO hydrogen peroxide-neutralizing agent was used oxidize broad range racemic (hetero)benzylic into prochiral ketones quantitively (>99% conv.). The situ formed carbonyl compounds were subsequently converted corresponding chiral via biocatalytic transhydrogenation catalyzed by lyophilized E. coli cells overexpressing highly stereoselective stereocomplementary recombinant alcohol dehydrogenases (ADHs) originated from Rhodococcus ruber (E. coli/ADH-A) or erythropolis coli/ReADH) obtain (S)-alcohols Lactobacillus kefir coli/Lk-ADH) KRED-110 (R)-alcohols, respectively. Overall, elaborated deracemization using 9-fluorenone-O2-blue LED-DMSO-E. coli/ADH carried out semipreparative scale (0.25 mmol; 63 mM final conc. 4 mL) at room temperature yielded aryl 82–99.9% conv., up 92% isolated yield, 97–99.9% ee complementary chirality.

Language: Английский

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Asymmetric Synthesis of Fused-Ring Tetrahydroisoquinolines and Tetrahydro-β-carbolines from 2-Arylethylamines via a Chemoenzymatic Approach

Organic Letters, Journal Year: 2022, Volume and Issue: 24(36), P. 6531 - 6536

Published: Sept. 6, 2022

While chiral fused-ring tetrahydroisoquinoline (THIQ) and tetrahydro-β-carboline (THβC) scaffolds have attracted considerable interest due to their wide spectrum of biological activities, the synthesis optically pure THIQs THβCs remains a challenging task. Herein, group active imine reductases were identified convert precursors into corresponding enantiocomplementary with high enantioselectivity conversion, establishing an efficient green chemoenzymatic approach alkaloids from 2-arylethylamines.

Language: Английский

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Chemoenzymatic synthesis

Communications Chemistry, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 13, 2025

Communications Chemistry is pleased to introduce a Collection of research works focused on recent developments within the interdisciplinary field chemoenzymatic synthesis. Here, Guest Editors highlight key themes and look towards future this field.

Language: Английский

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Crystallization Assisted Dynamic Kinetic Resolution for the Synthesis of (R)‐β‐Methylphenethylamine

ChemBioChem, Journal Year: 2024, Volume and Issue: 25(16)

Published: April 11, 2024

This study explores a combination of the concept enantioselective enzymatic synthesis β-chiral amines through transamination with in situ product crystallization (ISPC) to overcome inhibition. Using 2-phenylpropanal as readily available and easily racemizing substrate choice, (R)-β-methylphenethylamine ((R)-2-phenylpropan-1-amine) concentrations up 250 mM enantiomeric excesses 99 % are achieved when using commercially transaminase from Ruegeria pomeroyi fed-batch based dynamic kinetic resolution reaction on preparative scale. The source decomposition during is also investigated resulting unwanted byproduct formation successfully reduced insignificant levels.

Language: Английский

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Advanced Technologies for Large Scale Supply of Marine Drugs

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(2), P. 69 - 69

Published: Feb. 7, 2025

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure reliable sustainable supply marine natural products (MNPs) for their translation into commercial drugs other products. From structural point view few exceptions, MNPs pharmaceutical importance derive from the so-called secondary metabolism organisms. When production strategies rely on macroorganisms, harvesting or culturing coupled extraction procedures frequently remain only alternative producing these compounds an industrial scale. Their can often be implemented laboratory scale cultures bacterial, fungal, microalgal sources. However, diverse approach, combining traditional methods modern synthetic biology biosynthesis strategies, must considered invertebrate MNPs, as they are usually naturally accumulated in very small quantities. This review offers comprehensive examination various addressing challenges related supply, synthesis, scalability. also underscores recent biotechnological advancements that likely transform current industrial-scale manufacturing pharmaceuticals derived

Language: Английский

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Unravelling the C-C and C-N coupling mechanism for the CYP96T1-catalyzed biosynthesis of Amaryllidaceae alkaloids

Molecular Catalysis, Journal Year: 2023, Volume and Issue: 550, P. 113609 - 113609

Published: Oct. 7, 2023

Language: Английский

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Biocatalytic Cascades toward Iminosugar Scaffolds Reveal Promiscuous Activity of Shikimate Dehydrogenases

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(1), P. 103 - 108

Published: Jan. 11, 2023

Iminosugar scaffolds are highly sought-after pharmaceutical targets, but their chemical synthesis is lengthy and can suffer from poor scalability purification. Here we report protecting-group-free chemoenzymatic biocatalytic cascades to synthesize iminosugars sugar-derived aminopolyols in two steps. Using galactose oxidase variant F2 followed by a or enzymatic reduction provided an efficient one-pot route these with product formation >70%. Key success of this strategy was the application genome mining, which identified bacterial shikimate dehydrogenases as promiscuous iminosugar reductases. The cell-free protocols allowed for isolation polar products biotransformations single step through development gradient-elution cation exchange two-step pathway provides short synthetic that be used platform broader synthesis.

Language: Английский

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