Photobiocatalytic Strategies for Organic Synthesis

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(9), P. 5459 - 5520

Published: April 28, 2023

Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated most reactions involve molecules operating from their ground states. Over the past 25 years, there been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic a diverse array of reaction mechanisms are complementary to one another. This comprehensive review will describe state-of-the-art strategies photobiocatalysis synthesis until December 2022. Apart reviewing relevant literature, central goal this is delineate mechanistic differences between general employed field. We organize based on relationship photochemical step and transformations. The include studies, substrate scopes, protein optimization strategies. By clearly defining mechanistically-distinct chemistry, we hope illuminate future synthetic opportunities area.

Language: Английский

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Flavoprotein monooxygenases: Versatile biocatalysts

Biotechnology Advances, Journal Year: 2021, Volume and Issue: 51, P. 107712 - 107712

Published: Feb. 15, 2021

Flavoprotein monooxygenases (FPMOs) are single- or two-component enzymes that catalyze a diverse set of chemo-, regio- and enantioselective oxyfunctionalization reactions. In this review, we describe how FPMOs have evolved from model in mechanistic flavoprotein research to biotechnologically relevant catalysts can be applied for the sustainable production valuable chemicals. After historical account development FPMO field, explain classification system, which is primarily based on protein structural properties electron donor specificities. We then summarize most appealing reactions catalyzed by each group with focus different types oxygenation chemistries. Wherever relevant, report engineering strategies been used improve robustness applicability FPMOs.

Language: Английский

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The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 715 - 735

Published: Feb. 27, 2023

Biocatalysis is a highly valued enabling technology for pharmaceutical research and development as it can unlock synthetic routes to complex chiral motifs with unparalleled selectivity efficiency. This perspective aims review recent advances in the implementation of biocatalysis across early late-stage focus on processes preparative-scale syntheses.

Language: Английский

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Learning from Protein Engineering by Deconvolution of Multi‐Mutational Variants

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(36)

Published: June 17, 2024

Abstract This review analyzes a development in biochemistry, enzymology and biotechnology that originally came as surprise. Following the establishment of directed evolution stereoselective enzymes organic chemistry, concept partial or complete deconvolution selective multi‐mutational variants was introduced. Early experiments led to finding mutations can interact cooperatively antagonistically with one another, not just additively. During past decade, this phenomenon shown be general. In some studies, molecular dynamics (MD) quantum mechanics/molecular mechanics (QM/MM) computations were performed order shed light on origin non‐additivity at all stages an evolutionary upward climb. Data used construct unique multi‐dimensional rugged fitness pathway landscapes, which provide mechanistic insights different from traditional landscapes. Along related line, biochemists have long tested result introducing two point enzyme for reasons, followed by comparison respective double mutant so‐called cycles, showed only additive effects, but more recently also uncovered cooperative antagonistic non‐additive effects. We conclude suggestions future work, call unified overall picture epistasis.

Language: Английский

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Bioinspired Nanochitin‐Based Porous Constructs for Light‐Driven Whole‐Cell Biotransformations

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Solid‐state photosynthetic cell factories (SSPCFs) are a new production concept that leverages the innate abilities of microbes to drive valuable chemicals. It addresses practical challenges such as high energy and water demand improper light distribution associated with suspension‐based culturing; however, these systems often face significant related mass transfer. The approach focuses on overcoming limitations by carefully engineering microstructure immobilization matrix through freeze‐induced assembly nanochitin building blocks. use nanochitins optimized size enabled formation macropores lamellar spatial organization, which significantly improves transmittance distribution, crucial for maximizing efficiency reactions. biomimetic crosslinking strategy, leveraging specific interactions between polyphosphate anions primary amine groups featured chitin fibers, produced mechanically robust wet‐resilient cryogels maintained their functionality under operational conditions. Various model biotransformation reactions leading value‐added chemicals performed in chitin‐based matrix. demonstrates superior or comparable performance existing state‐of‐the‐art matrices systems. findings suggest cryogel holds promise advancing development solid‐state factories, offering scalable solution improve productivity light‐driven biotransformation.

Language: Английский

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P450-driven plastic-degrading synthetic bacteria

Trends in biotechnology, Journal Year: 2021, Volume and Issue: 40(2), P. 166 - 179

Published: July 7, 2021

Language: Английский

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Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(11), P. 4739 - 4745

Published: March 8, 2022

We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity engineered "carbene transferase" enzymes. A laboratory-evolved variant cytochrome P450BM3, P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over [1,2]-Stevens rearrangement but also overrides the inherent reactivity aziridinium ylides, cheletropic extrusion olefins, perform rearrangement. By controlling fate highly reactive ylide intermediates, these evolvable biocatalysts promote transformation which cannot currently be performed using other catalyst classes.

Language: Английский

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Evolution of enzyme functionality in the flavin-containing monooxygenases

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

Published: Feb. 24, 2023

Abstract Among the molecular mechanisms of adaptation in biology, enzyme functional diversification is indispensable. By allowing organisms to expand their catalytic repertoires and adopt fundamentally different chemistries, animals can harness or eliminate new-found substances xenobiotics that they are exposed new environments. Here, we explore flavin-containing monooxygenases (FMOs) essential for xenobiotic detoxification. Employing a paleobiochemistry approach combination with enzymology techniques disclose set historical substitutions responsible family’s tetrapods. Remarkably, few amino acid replacements differentiate an ancestral multi-tasking FMO into more specialized monooxygenase by modulating oxygenating flavin intermediate. Our findings substantiate ongoing premise enzymatic function hinges on subset residues not limited active site core.

Language: Английский

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Enzymatic Assembly of Diverse Lactone Structures: An Intramolecular C–H Functionalization Strategy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1580 - 1587

Published: Jan. 2, 2024

Lactones are cyclic esters with extensive applications in materials science, medicinal chemistry, and the food perfume industries. Nature's strategy for synthesis of many lactones found natural products always relies on a single type retrosynthetic strategy, C–O bond disconnection. Here, we describe set laboratory-engineered enzymes that use new-to-nature C–C bond-forming to assemble diverse lactone structures. These engineered "carbene transferases" catalyze intramolecular carbene insertions into benzylic or allylic C–H bonds, which allow different ring sizes scaffolds from simple starting materials. Starting serine-ligated cytochrome P450 variant previously other carbene-transfer activities, directed evolution generated P411-LAS-5247, exhibits high activity constructing five-membered ε-lactone, lactam, ketone (up 5600 total turnovers (TTN) >99% enantiomeric excess (ee)). Further engineering led variants P411-LAS-5249 P411-LAS-5264, deliver six-membered δ-lactones seven-membered ε-lactones, respectively, overcoming thermodynamically unfavorable strain associated these compared γ-lactones. This new was further extended complex based fused, bridged, spiro rings. The enzymatic platform developed here complements biosynthetic strategies assembly expands structural diversity accessible through functionalization.

Language: Английский

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Photoinduced Promiscuity of Cyclohexanone Monooxygenase for the Enantioselective Synthesis of α‐Fluoroketones

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(50)

Published: Oct. 19, 2022

The development of mild, efficient, and enantioselective methods for preparing chiral fluorinated compounds has been a long-standing challenge. Herein, we report promiscuous cyclohexanone monooxygenase (CHMO) the photoinduced synthesis α-fluoroketones via reductive dehalogenation α,α-halofluoroketones. Wild-type CHMO from Acinetobacter sp. possesses this ability innately; however, yield stereoselectivity are low. A structure-guided rational design improved remarkably. Mechanistic studies molecular simulations demonstrated that catalyzes novel electron transfer (ET)/proton (PT) mechanism, distinct previously reported reductases with similar promiscuity. This methodology was expanded to various substrates, desirable were obtained in high yields (up 99 %) e.r. values 99:1).

Language: Английский

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