Enantioselective [2+2]-cycloadditions with triplet photoenzymes

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 715 - 720

Published: Sept. 21, 2022

Language: Английский

---

Stereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis

Science, Journal Year: 2023, Volume and Issue: 381(6656), P. 444 - 451

Published: July 27, 2023

Developing synthetically useful enzymatic reactions that are not known in biochemistry and organic chemistry is an important challenge biocatalysis. Through the synergistic merger of photoredox catalysis pyridoxal 5'-phosphate (PLP) biocatalysis, we developed a radical biocatalysis approach to prepare valuable noncanonical amino acids, including those bearing stereochemical dyad or triad, without need for protecting groups. Using engineered PLP enzymes, either enantiomeric product could be produced biocatalyst-controlled fashion. Synergistic

Language: Английский

---

Photochemical iron-catalyzed decarboxylative azidation via the merger of ligand-to-metal charge transfer and radical ligand transfer catalysis

Chem Catalysis, Journal Year: 2023, Volume and Issue: 3(6), P. 100603 - 100603

Published: April 12, 2023

Language: Английский

---

Direct visible-light-excited flavoproteins for redox-neutral asymmetric radical hydroarylation

Nature Catalysis, Journal Year: 2023, Volume and Issue: 6(11), P. 996 - 1004

Published: Sept. 14, 2023

Language: Английский

---

Single-Atom Nanozymes: From Precisely Engineering to Extensive Applications

Accounts of Materials Research, Journal Year: 2024, Volume and Issue: 5(3), P. 347 - 357

Published: Feb. 3, 2024

ConspectusNanozymes are nanomaterials with intrinsic enzyme-like properties that can overcome the current limitations of natural enzymes, such as high preparation cost, instability, restricted application scenarios, etc. Since Fe3O4 nanoparticles (NPs) were shown to possess peroxidase (POD)-like activity in 2007, thousands reported mimic catalytic various types enzymes including catalase (CAT), haloperoxidase, superoxide dismutase (SOD), glucose oxidase, glutathione peroxidase, hydrolase, nuclease, nitroreductase, and others. Particularly, some nanozymes showed multienzyme-like activities regarding changes scenarios temperature, pH, Benefiting from their distinct physical-chemical characteristics properties, have been widely applied biomedical related fields vitro detections vivo therapeutic treatments. However, currently ambiguous structure–function correlations relatively inferior compared promote extensive efforts for modifications on development novel alternative nanozymes. The single-atom (SAzymes) present a unique way highly evolved enzyme active centers, because atomically dispersed sites, which leads atom utilization efficiency and, thus, potentially extraordinary activity. Also, abilities modify centers and/or tune interactions between metal supporting ligands provide precise engineer SAzymes at atomic levels. Given well-defined geometric electronic structures, thus serve exceptional templates deciphering relationships, is beneficial further improving performances.In this Account, we will review our recent other notable works developments effective mimics applications areas. We begin brief introduction why emergence SAzymes, artificial enzyme, tackles challenges facing. Next, focus systematic design, synthesis optimization especially impacts engineering environment an enzymologist perspective. For example, alternations first-shell ligand N P/S, SAzymes' CAT-like increased more than 4-fold. coordination numbers (x) Co–Nx(C) SAzyme significantly altered its oxidase (OXD)-like kinetics Then, discuss ways standardization specific kinetics. also wide ranges colorimetric biologicals, antibiosis treatments, cancer therapies. Finally, address future perspectives

Language: Английский

---

Engineering non-haem iron enzymes for enantioselective C(sp3)–F bond formation via radical fluorine transfer

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(8), P. 958 - 966

Published: March 28, 2024

Language: Английский

---

From Ground-State to Excited-State Activation Modes: Flavin-Dependent “Ene”-Reductases Catalyzed Non-natural Radical Reactions

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(9), P. 1446 - 1457

Published: April 11, 2024

ConspectusEnzymes are desired catalysts for chemical synthesis, because they can be engineered to provide unparalleled levels of efficiency and selectivity. Yet, despite the astonishing array reactions catalyzed by natural enzymes, many reactivity patterns found in small molecule have no counterpart living world. With a detailed understanding mechanisms utilized catalysts, we identify existing enzymes with potential catalyze that currently unknown nature. Over past eight years, our group has demonstrated flavin-dependent "ene"-reductases (EREDs) various radical-mediated selectivity, solving long-standing challenges asymmetric synthesis.This Account presents development EREDs as general radical reactions. While developed multiple generating radicals within protein active sites, this account will focus on examples where flavin mononucleotide hydroquinone (FMNhq) serves an electron transfer initiator. initial mechanistic hypotheses were rooted electron-transfer-based initiation commonly used synthetic organic chemists, ultimately uncovered emergent unique site. We begin covering intramolecular discussing how activates substrate reduction altering redox-potential alkyl halides templating charge complex between flavin-cofactor. Protein engineering been modify fundamental photophysics these reactions, highlighting opportunity tune systems further using directed evolution. This section highlights range coupling partners termination available reactions.The next intermolecular role enzyme-templated ternary complexes among cofactor, halide, partner gating ensure it only occurs when both substrates bound highlight applications activation mode, including olefin hydroalkylation, carbohydroxylation, arene functionalization, nitronate alkylation. also discusses favor steps elusive solution reductive nitroalkanes. aware several recent EREDs-catalyzed photoenzymatic transformations from other groups. discuss results papers context nuances substrates.These biocatalytic often complement state-of-the-art small-molecule-catalyzed making valuable addition chemist's toolbox. Moreover, underlying principles studied potentially operative cofactor-dependent proteins, opening door different types enzyme-catalyzed anticipate serve guide inspire broad interest repurposing access new transformations.

Language: Английский

---

Stereodivergent photobiocatalytic radical cyclization through the repurposing and directed evolution of fatty acid photodecarboxylases

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1339 - 1347

Published: April 17, 2024

Language: Английский

---

Biocatalytic enantioselective C(sp3)–H fluorination enabled by directed evolution of non-haem iron enzymes

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(8), P. 967 - 975

Published: April 26, 2024

Language: Английский

---

Asymmetric C-Alkylation of Nitroalkanes via Enzymatic Photoredox Catalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(2), P. 787 - 793

Published: Jan. 6, 2023

Tertiary nitroalkanes and the corresponding α-tertiary amines represent important motifs in bioactive molecules natural products. The C-alkylation of secondary with electrophiles is a straightforward strategy for constructing tertiary nitroalkanes; however, controlling stereoselectivity this type reaction remains challenging. Here, we report highly chemo- stereoselective alkyl halides catalyzed by an engineered flavin-dependent "ene"-reductase (ERED). Directed evolution old yellow enzyme from Geobacillus kaustophilus provided triple mutant, GkOYE-G7, capable synthesizing high yield enantioselectivity. Mechanistic studies indicate that excitation enzyme-templated charge-transfer complex formed between substrates cofactor responsible radical initiation. Moreover, single-enzyme two-mechanism cascade was developed to prepare simple nitroalkenes, highlighting potential use one two mechanistically distinct reactions.

Language: Английский

---