Biocatalytic stereocontrolled head-to-tail cyclizations as a tool for streamlined hybrid synthesis of terpenes DOI Creative Commons
Bernhard Hauer, Andreas Schneider,

Thomas B. Lystbæk

et al.

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

Published: Sept. 18, 2023

Abstract The stereocontrolled cationic cyclization cascade is a vital step in the modular biogenesis of terpenes, as it defines carbon skeleton's three-dimensional structure one atom-economical step. While nature has adopted this strategy for eons, state-of-the-art synthetic routes to asymmetrically access cyclic terpenes still rely predominantly on sequential multi-step scaffold remodelling few abundant precursors. Herein, we bridge long-standing methodological gap and demonstrate target-oriented synthesis ability squalene-hopene cyclase. Our mechanistic insights show that biocatalytic head-to-tail highly customizable by mechanism-guided enzyme engineering substrate-focused setup engineering. As result, two- or three-step hybrid pheromones, fragrances, drug candidates merging with interdisciplinary catalytic methods. This biomimetic significantly reduces effort provides rapid thousands head-to-tail-fused scaffolds.

Language: Английский

An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,β‐Unsaturated Aldehydes—Design and Evolution DOI
Mingzhu Yu, Ye Yuan, Zhenjie Li

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(25)

Published: April 10, 2024

The introduction of an abiological catalytic group into the binding pocket a protein host allows for expansion enzyme chemistries. Here, we report generation artificial by genetic encoding non-canonical amino acid that contains secondary amine side chain. and function synergistically to catalyze asymmetric nitrocyclopropanation α,β-unsaturated aldehydes iminium activation mechanism. designer was evolved optimal variant catalyzes reaction at high conversions with diastereo- enantioselectivity. This work demonstrates application code in design expands scope enzyme-catalyzed reactions.

Language: Английский

Citations

7
Biocatalytic stereocontrolled head-to-tail cyclizations of unbiased terpenes as a tool in chemoenzymatic synthesis DOI Creative Commons
Andreas Schneider,

Thomas B. Lystbæk,

Daniel Markthaler

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 10, 2024

Language: Английский

Citations

2
An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,β‐Unsaturated Aldehydes—Design and Evolution DOI
Mingzhu Yu, Ye Yuan, Zhenjie Li

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(25)

Published: April 10, 2024

Abstract The introduction of an abiological catalytic group into the binding pocket a protein host allows for expansion enzyme chemistries. Here, we report generation artificial by genetic encoding non‐canonical amino acid that contains secondary amine side chain. and function synergistically to catalyze asymmetric nitrocyclopropanation α,β‐unsaturated aldehydes iminium activation mechanism. designer was evolved optimal variant catalyzes reaction at high conversions with diastereo‐ enantioselectivity. This work demonstrates application code in design expands scope enzyme‐catalyzed reactions.

Language: Английский

Citations

1
Unified Enantiospecific Synthesis of Drimane Meroterpenoids Enabled by Enzyme Catalysis and Transition Metal Catalysis DOI Creative Commons
Yipeng You, Xuejie Zhang,

Wen Xiao

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(46), P. 19307 - 19314

Published: Jan. 1, 2024

A unified synthetic strategy for drimane meroterpenoids was developed by combining heterologous biosynthesis, enzymatic oxidation, and transition metal catalysis. Six were synthesized in a concise enantiospecific manner.

Language: Английский

Citations

1
Harnessing the catalytic plasticity of the ent-kaurene synthase from Bradyrhizobium japonicum to produce the ent-rosane and ent-pimarane scaffolds DOI
Fan Zhang, Sujing Wang, Wen Xiao

et al.

Catalysis Science & Technology, Journal Year: 2023, Volume and Issue: 14(2), P. 306 - 314

Published: Nov. 30, 2023

The F72Y mutation of the ent -kaurene synthase from Bradyrhizobium japonicum leads to formation -rosa-5(10),15-diene and -pimara-8,15-diene, two common scaffolds labdane diterpenoids.

Language: Английский

Citations

3
Biocatalytic stereocontrolled head-to-tail cyclizations as a tool for streamlined hybrid synthesis of terpenes DOI Creative Commons
Bernhard Hauer, Andreas Schneider,

Thomas B. Lystbæk

et al.

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

Published: Sept. 18, 2023

Abstract The stereocontrolled cationic cyclization cascade is a vital step in the modular biogenesis of terpenes, as it defines carbon skeleton's three-dimensional structure one atom-economical step. While nature has adopted this strategy for eons, state-of-the-art synthetic routes to asymmetrically access cyclic terpenes still rely predominantly on sequential multi-step scaffold remodelling few abundant precursors. Herein, we bridge long-standing methodological gap and demonstrate target-oriented synthesis ability squalene-hopene cyclase. Our mechanistic insights show that biocatalytic head-to-tail highly customizable by mechanism-guided enzyme engineering substrate-focused setup engineering. As result, two- or three-step hybrid pheromones, fragrances, drug candidates merging with interdisciplinary catalytic methods. This biomimetic significantly reduces effort provides rapid thousands head-to-tail-fused scaffolds.

Language: Английский

Citations

0