A Microbial Cell Factory Combining an Artificial Metathase with a Fatty Acid Decarboxylase for New-to-Nature Synthesis of Cycloalkenes DOI Creative Commons
Thomas R. Ward, Zhi Zou, Shuke Wu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

Abstract Artificial metalloenzymes (ArMs) are powerful tools for catalyzing new-to-nature reactions. ArMs offer great potential to complement natural enzymes in concurrent cascade For in cellulo applications, however, the abundance of thiols cytosol aerobic organisms limits use that rely on precious metal cofactors. To overcome this limitation, compartmentalization either periplasm or surface Escherichia coli has shown promise. We report herein our efforts combine a surface-displayed artificial metathase with UndB, an inner membrane decarboxylase. The resulting converts medium-chain dicarboxylates cyclic alkenes. optimize cascade, we evolved both independently and fine-tuned their relative expression levels. Compared wild-type whole-cell enzyme engineered strain was improved by > 75-fold conversion sebacic acid cyclohexene. best knowledge, represents first example combines ArM.

Language: Английский

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

Daniel J. Wackelin,

Runze Mao, Kathleen M. Sicinski

et al.

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

Citations

19
Enzyme engineering for biocatalysis DOI Creative Commons
Caroline E. Paul, Ulf Hanefeld, Frank Hollmann

et al.

Molecular Catalysis, Journal Year: 2024, Volume and Issue: 555, P. 113874 - 113874

Published: Jan. 31, 2024

Contemporary Biocatalysis heavily relies on enzyme engineering as natural enzymes frequently lack the requisite attributes for effective organic synthesis. The inherent limitations in stability, catalytic activity, and selectivity of wild-type often hinder their suitability chemical Over past 25 years, there has been an unprecedented advancement protein tools, empowering enzymologists to customise precisely meet demands In this discussion, we delineate some most crucial techniques significance facilitating

Language: Английский

Citations

14
Chiral Osmium(II)/Salox Species Enabled Enantioselective γ‐C(sp3)−H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development DOI
Weijie Chen, Huiying Xu,

Fu‐Xiaomin Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(20)

Published: March 19, 2024

Abstract Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp 3 )−H functionalization, among which Os(II)/Salox species is found be most efficient for precise stereocontrol in realizing amidation. As exemplified by enantioenriched pyrrolidinone synthesis, such tailored catalyst efficiently enables an intramolecular site‐/enantioselective amidation γ‐position dioxazolone substrates, benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording corresponding γ‐lactam products with good er values (up 99 : 1) diverse functionality (>35 examples). The unique performance advantage developed system terms catalytic energy profile induction has further clarified integrated experimental computational studies.

Language: Английский

Citations

5
Combining an artificial metathase with a fatty acid decarboxylase in a whole cell for cycloalkene synthesis DOI
Zhi Zou, Shuke Wu, Daniel Gerngross

et al.

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(9), P. 1113 - 1123

Published: June 27, 2024

Language: Английский

Citations

3
Mechanistic and Computational Insights into Asymmetric Intramolecular Iron-Catalyzed Nitrene Transfer into Benzylic C–H Bonds DOI
Kyeongdeok Seo, Yu Zhang, Tuấn Anh Trịnh

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 3789 - 3798

Published: Feb. 18, 2025

Language: Английский

Citations

0
Enzyme-Like Activity Artificial Metalloenzymes DOI
Carla Garcia‐Sanz, José M. Palomo

Topics in organometallic chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Enzyme-Controlled Bidirectional Enantioselectivity in Asymmetric Decarboxylative Mannich Reaction for Synthesizing β-Sulfonamide Ketones DOI
Yong Tang, Yaning Xu, Xuan Zhang

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4784 - 4797

Published: March 6, 2025

Language: Английский

Citations

0
Engineering metalloenzymes for new-to-nature carbene and nitrene transfer biocatalysis DOI
Weitao Pan, Xinlong Fan, Wei Jiang

et al.

CHINESE JOURNAL OF CATALYSIS (CHINESE VERSION), Journal Year: 2025, Volume and Issue: 72, P. 4 - 23

Published: May 1, 2025

Language: Английский

Citations

0
Cp*Ir(III)-Catalyzed Asymmetric Tandem Intramolecular Aziridination/Aza-Semipinacol Rearrangement of Alkenyl 1,4,2-Dioxazol-5-one DOI
Mengbo Wu, Yuanzhen Xu,

Songlin Bai

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 10310 - 10319

Published: June 2, 2025

Language: Английский

Citations

0
Recent advances in the design and optimization of artificial metalloenzymes DOI
Iori Morita, Thomas R. Ward

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 81, P. 102508 - 102508

Published: Aug. 1, 2024

Language: Английский

Citations

3