Biocatalytic Strategies for Nitration Reactions DOI Creative Commons
Xiling Wang, Matteo Aleotti, Mélanie Hall

и другие.

JACS Au, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Nitro compounds are key synthetic intermediates used as enabling tools in synthesis and found a large range of essential compounds, including pharmaceuticals, pesticides, various organic dyes. Despite recent methodological developments, the industrial preparation nitro still suffers from harsh reaction conditions, along with poor selectivity problematic environmental footprint. Although biological enzymatic methods exist, mild approaches for bionitration underexplored. Enzymes, their exquisite compatibility have potential to revolutionize way prepared. In this perspective, we systematically analyze currently available biological/enzymatic methods, oxidation an amine precursor or consisting direct oxidative nitration non-oxidative nitration. By examining both scope mechanism these reactions, aim present update on state-of-the-art while highlighting current challenges emerging field. The goal perspective is inspire innovation sustainable synthesis, providing chemists valuable guide.

Язык: Английский

Semirationally Engineering an Efficient P450 Peroxygenase for Regio- and Enantioselective Hydroxylation of Steroids DOI
Shengxian Fan, Mingming Qin, Qian Wang

и другие.

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 2977 - 2986

Опубликована: Фев. 5, 2025

Язык: Английский

Процитировано

4
Emerging Strategies for Modifying Cytochrome P450 Monooxygenases into Peroxizymes DOI
Shengxian Fan, Zhiqi Cong

Accounts of Chemical Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 31, 2024

ConspectusCytochrome P450 monooxygenase is a versatile oxidizing enzyme with great potential in synthetic chemistry and biology. However, the dependence of its catalytic function on nicotinamide cofactor NAD(P)H redox partner proteins limits practical application vitro. An alternative to expensive cofactors low-cost H2O2, which can be used directly exploit P450s. peroxide shunt pathway generally inefficient at driving catalysis compared normal NAD(P)H-dependent activity. Over last few decades, scientific community has made continuous efforts use directed evolution or site-directed mutagenesis modify monooxygenases into their peroxizyme modes─peroxygenase peroxidase. Despite significant progress, obtaining efficient peroxizymes remains huge challenge. Here, we summarize our modulate activity applications challenging selective C–H oxidation, oxygenation, oxyfunctionalization over past seven years. We first developed dual-functional small molecule (DFSM) strategy for transforming P450BM3 peroxygenase. In this strategy, typical DFSM, such as N-(ω-imidazolyl)-hexanoyl-l-phenylalanine (Im-C6-Phe), binds protein an anchoring group one end plays general acid–base role activation H2O2 imidazolyl other end. Compared O–O homolysis mechanism absence addition DFSM efficiently enables heterolytic cleavage adduct Fe–O–OH, thus being favored formation active species compound I, been demonstrated by combining crystallographic theoretical calculations. Furthermore, engineering showed unique performance DFSM-facilitated peroxygenase highly difficult oxidation bonds. This was during chemoselective hydroxylation gaseous alkanes, regioselective O-demethylation aryl ethers, (R)-enantioselective epoxidation styrene, regio- enantiomerically diverse alkylbenzenes. Second, that could effectively switched peroxidase mode through mechanism-guided redox-sensitive residues. Utilizing enabled direct nitration unsaturated hydrocarbons including phenols, aromatic amines, styrene derivatives, not only P450-catalyzed phenols amines time but also example biological olefins. Finally, report tunnel enable several different time, providing approach accessing engineered peroxygenases. Account, highlight emerging strategies have producing biocatalysts. Although primarily applied date, both residue show extend These expanded scope catalysis. Additionally, they provide solution inert bonds chemistry.

Язык: Английский

Процитировано

17
Tuning the peroxidase activity of artificial P450 peroxygenase by engineering redox-sensitive residues DOI

Feng-Jie Jiang,

Z. Jane Wang,

Zhiqi Cong

и другие.

Faraday Discussions, Год журнала: 2024, Номер 252, С. 52 - 68

Опубликована: Янв. 1, 2024

Engineering redox-sensitive residues dramatically increases the peroxidase activity of P450BM3 monooxygenase, providing new insights and a strategy for regulating P450s' promiscuous functionality.

Язык: Английский

Процитировано

3
Molecularly Imprinted Polymers for Highly Specific Bioorthogonal Catalysis Inside Cells DOI

Zhiguo Gao,

Quanlin Shao,

Jiaqi Xing

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(49)

Опубликована: Авг. 5, 2024

Abstract Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight potential molecularly imprinted enzyme mimics (MIEs) containing Cu center specific substrate binding domain, for conducing dimethylpropargyloxycarbonyl (DmProc) cleavage reactions Our studies reveal Cu‐MIEs act as highly guides, precisely catalyzing target substrates, even in glutathione (GSH)‐rich cellular environments. By adapting templates similar to evolved activity high level provided method broaden its scope other unique substrates. This system was applied thyroid hormone (T3)‐responsive gene switch model, inducing firefly luciferase expression by T3 approach verifies MIEs effectively rescue DmProc‐bearing prodrugs seamlessly integrating themself into biocatalytic networks.

Язык: Английский

Процитировано

2
Diverse N‐Oxidation of Primary Aromatic Amines Controlled by Engineered P450 Peroxizyme Variants Facilitated by Dual‐Functional Small Molecule DOI Creative Commons
Jie Chen,

Fuquan Yao,

Yiping Jiang

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Abstract Amine oxidation is an important organic reaction for the production of high‐value N ‐containing compounds. However, it still challenging to control reactivity active ‐centered radicals selectively access ‐oxidation products. Herein, this study reports engineering cytochrome P450BM3 into multifunctional ‐oxidizing enzymes with assistance dual‐functional small molecules (DFSM) produce ‐oxygenation (i.e., p ‐nitrosobenzene, ‐nitrobenzene, and azoxybenzene) one‐electron products oligomeric quinones azobenzene) from aromatic amines. The best mutant, F87A/T268V/V78T/A82T, exclusively gives ‐nitrosobenzene (up 98% selectivity), whereas selectivity ‐nitrobenzene >99% using mutant F87A/T268V/A82T/I263L. Crystal structure analysis reveals that key mutations DFSM exert synergistic effects on catalytic promiscuity by controlling substrate orientation in center. This highlights potential DFSM‐facilitated P450 peroxygenase peroxidase synthesis compounds via controllable amines, substantially expanding chemical space enzymes.

Язык: Английский

Процитировано

1
Molecularly Imprinted Polymers for Highly Specific Bioorthogonal Catalysis inside Cells DOI

Zhiguo Gao,

Quanlin Shao,

Jiaqi Xing

и другие.

Angewandte Chemie, Год журнала: 2024, Номер 136(49)

Опубликована: Авг. 5, 2024

Abstract Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight potential molecularly imprinted enzyme mimics (MIEs) containing Cu center specific substrate binding domain, for conducing dimethylpropargyloxycarbonyl (DmProc) cleavage reactions Our studies reveal Cu‐MIEs act as highly guides, precisely catalyzing target substrates, even in glutathione (GSH)‐rich cellular environments. By adapting templates similar to evolved activity high level provided method broaden its scope other unique substrates. This system was applied thyroid hormone (T3)‐responsive gene switch model, inducing firefly luciferase expression by T3 approach verifies MIEs effectively rescue DmProc‐bearing prodrugs seamlessly integrating themself into biocatalytic networks.

Язык: Английский

Процитировано

0
Hemoglobin: An efficient oxidase for the green synthesis of quinazoline derivatives by biocatalytic domino strategy DOI
Sheng Xie,

Chenyi Zhang,

Ye Dai

и другие.

Molecular Catalysis, Год журнала: 2024, Номер 570, С. 114680 - 114680

Опубликована: Ноя. 21, 2024

Язык: Английский

Процитировано

0
Biocatalytic Strategies for Nitration Reactions DOI Creative Commons
Xiling Wang, Matteo Aleotti, Mélanie Hall

и другие.

JACS Au, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Nitro compounds are key synthetic intermediates used as enabling tools in synthesis and found a large range of essential compounds, including pharmaceuticals, pesticides, various organic dyes. Despite recent methodological developments, the industrial preparation nitro still suffers from harsh reaction conditions, along with poor selectivity problematic environmental footprint. Although biological enzymatic methods exist, mild approaches for bionitration underexplored. Enzymes, their exquisite compatibility have potential to revolutionize way prepared. In this perspective, we systematically analyze currently available biological/enzymatic methods, oxidation an amine precursor or consisting direct oxidative nitration non-oxidative nitration. By examining both scope mechanism these reactions, aim present update on state-of-the-art while highlighting current challenges emerging field. The goal perspective is inspire innovation sustainable synthesis, providing chemists valuable guide.

Язык: Английский

Процитировано

0