Synthetic biology 2020–2030: six commercially-available products that are changing our world

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Dec. 11, 2020

Synthetic biology will transform how we grow food, what eat, and where source materials medicines. Here I have selected six products that are now on the market, highlighting underlying technologies projecting forward to future can be expected over next ten years.

Language: Английский

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Directed evolution of enzymatic silicon-carbon bond cleavage in siloxanes

Science, Journal Year: 2024, Volume and Issue: 383(6681), P. 438 - 443

Published: Jan. 25, 2024

Volatile methylsiloxanes (VMS) are man-made, nonbiodegradable chemicals produced at a megaton-per-year scale, which leads to concern over their potential for environmental persistence, long-range transport, and bioaccumulation. We used directed evolution engineer variant of bacterial cytochrome P450

Language: Английский

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Enzymatic strategies for asymmetric synthesis

RSC Chemical Biology, Journal Year: 2021, Volume and Issue: 2(4), P. 958 - 989

Published: Jan. 1, 2021

Asymmetric synthesis achieved with enzymes for stereoselective reduction and bond forming reactions, enantioselective atroposelective reactions.

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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Caffeine Biodegradation by Cytochrome P450 1A2. What Determines the Product Distributions?

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(32)

Published: March 17, 2023

Caffeine is a natural compound found in plant seeds that after consumption by humans effects the central nervous system as well cardiovascular system. In general, cytochrome P450 enzymes liver are involved biodegradation of caffeine, which gives paraxanthine, theobromine and theophylline products. There has been debate for many years why multiple products obtained how their distributions determined. To this end we performed high-level computational study using combination molecular dynamics quantum mechanical approaches. A series chemical cluster models on mechanism caffeine activation model complexes give hydrogen atom abstraction barriers predicts correct ordering statistical distribution Our studies highlight second-coordination sphere thermochemical properties substrate determine product distributions.

Language: Английский

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How Does the Nonheme Iron Enzyme NapI React through l-Arginine Desaturation Rather Than Hydroxylation? A Quantum Mechanics/Molecular Mechanics Study

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(16), P. 10705 - 10721

Published: Aug. 1, 2023

The naphthyridinomycin biosynthesis enzyme NapI selectively performs the desaturation of a free l-arginine amino acid at C4–C5 bond as part its antibiotic reaction. This is an unusual reaction triggered by nonheme iron dioxygenase most l-Arg activating enzymes cause substrate hydroxylation aliphatic C–H bond; hence, this has great potential in biotechnology for efficient synthesis drug and fragrance molecules. However, reactions chemical catalysis are challenging to perform they often require toxic heavy metals solvents. Its enzymatic would provide environmentally benign alternative. To find biotechnological application NapI, we performed computational study on enzyme. catalytic mechanism controversial several possible mechanisms have been suggested via either radical or charge-transfer pathways. We set up structure from deposited crystal coordinates substrate-bound inserted co-substrate (α-ketoglutarate) solvated water environment. Thereafter, series quantum mechanics/molecular mechanics calculations validated results against experimental data. Subsequently, investigated leading C5- C4-hydroxylation C4–C5-desaturation give rate-determining hydrogen atom abstraction step that lowest C5–H position gives intermediate, although C4–H group less than ΔG = 2 kcal mol–1 higher energy. show isotopic substitution key bonds with C–D changes product distributions dramatically. C5 intermediate bifurcation pathways small second much OH rebound barrier. also located iron(II)-hydroxo species cationic substrate, but kinetics thermodynamics respect make it unviable mechanism. A comparison alternative hydroxylating identifies differences orientation positioning their coordination sphere interactions protein induces different dipole electric field direction. Our work shows governed substrate-binding polarity bonding pocket guides products locking iron(III)-hydroxo position. understanding given valuable insight into reactivity may help design engineer better highly selective processes biotechnology.

Language: Английский

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Chiral Iron Porphyrins Catalyze Enantioselective Intramolecular C(sp³)−H Bond Amination Upon Visible‐Light Irradiation

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(19)

Published: Jan. 30, 2023

Iron-catalyzed asymmetric amination of C(sp3 )-H bonds is appealing for synthetic applications due to the biocompatibility and high earth abundance iron, but examples such reactions are sparse. Herein we describe chiral iron complexes meso- β-substituted-porphyrins that can catalyze intramolecular aryl arylsulfonyl azides afford indolines (29 examples) benzofused cyclic sulfonamides (17 examples), respectively, with up 93 % ee (yield: 99 %) using 410 nm light under mild conditions. Mechanistic studies, including DFT calculations, reveal Fe(NSO2 Ar) intermediate generated in situ photochemical conditions reacts bond through a stepwise hydrogen atom transfer/radical rebound mechanism, enantioselectivity arising from cooperative noncovalent interactions between unit peripheral substituents porphyrin scaffold.

Language: Английский

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Catalytic Hydrogenolysis by Atomically Dispersed Iron Sites Embedded in Chemically and Redox Non-innocent N-Doped Carbon

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 8618 - 8629

Published: March 12, 2024

Atomically dispersed first-row transition metals embedded in nitrogen-doped carbon materials (M–N–C) show promising performance catalytic hydrogenation but are less well-studied for reactions with more complex mechanisms, such as hydrogenolysis. Their ability to catalyze selective C–O bond cleavage of oxygenated hydrocarbons aryl alcohols and ethers is enhanced the participation ligands directly bound metal ion well longer-range contributions from support. In this article, we describe how Fe–N–C catalysts well-defined local structures Fe sites The reaction facilitated by N–C According spectroscopic analyses, as-synthesized contain mostly pentacoordinated FeIII sites, four in-plane nitrogen donor one axial hydroxyl ligand. presence 20 bar H2 at 170–230 °C, ligand lost when N4FeIIIOH reduced N4FeII, assisted chemisorbed on When an alcohol binds tetracoordinated FeII homolytic O–H accompanied reoxidation H atom transfer role support hydrogenolysis analogous behavior chemically redox-non-innocent molecular based ions enhances M–N–Cs achieve types multistep activations strong bonds needed upgrade renewable recycled feedstocks.

Language: Английский

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Structural and Biochemical Studies Enlighten the Unspecific Peroxygenase from Hypoxylon sp. EC38 as an Efficient Oxidative Biocatalyst

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(18), P. 11511 - 11525

Published: Sept. 2, 2021

Unspecific peroxygenases (UPOs) are glycosylated fungal enzymes that can selectively oxidize C–H bonds. UPOs employ hydrogen peroxide as the oxygen donor and reductant. With such an easy-to-handle cosubstrate without need for a reducing agent, emerging convenient oxidative biocatalysts. Here, unspecific peroxygenase from Hypoxylon sp. EC38 (HspUPO) was identified in activity-based screen of six putative were heterologously expressed Pichia pastoris. The enzyme found to tolerate selected organic solvents acetonitrile acetone. HspUPO is versatile catalyst performing various reactions, oxidation prim- sec-alcohols, epoxidations, hydroxylations. Semipreparative biotransformations demonstrated nonenantioselective racemic 1-phenylethanol rac-1b (TON = 13 000), giving product with 88% isolated yield, indole 6a give indigo 6b 2800) 98% yield. features compact rigid three-dimensional conformation wraps around heme defines funnel-shaped tunnel leads iron protein surface. extends along distance about 12 Å fairly constant diameter its innermost segment. Its surface comprises both hydrophobic hydrophilic groups dealing substrates variable polarities. structural investigation several protein–ligand complexes revealed active site accessible molecules varying bulkiness minimal or no conformational changes, explaining relatively broad substrate scope enzyme. expression system, robust operational properties, small size, well-defined features, diverse reaction scope, exploitable candidate peroxygenase-based biocatalysis.

Language: Английский

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Negative catalysis / non-Bell-Evans-Polanyi reactivity by metalloenzymes: Examples from mononuclear heme and non-heme iron oxygenases

Coordination Chemistry Reviews, Journal Year: 2021, Volume and Issue: 439, P. 213914 - 213914

Published: April 15, 2021

Language: Английский

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