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

Protein Engineering of Substrate Specificity toward Nitrilases: Strategies and Challenges DOI

Shi-Qian Bian,

Zi-Kai Wang,

Jin‐Song Gong

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Nitrilase is extensively applied across diverse sectors owing to its unique catalytic properties. Nevertheless, in industrial production, nitrilases often face issues such as low efficiency, limited substrate range, suboptimal selectivity, and side reaction products, which have garnered heightened attention. With the widespread recognition that structure of enzymes has a direct impact on their properties, an increasing number researchers are beginning optimize functional characteristics by modifying structures, order meet specific or biotechnology application needs. Particularly artificial intelligence era, innovative computer-aided design enzyme engineering offers remarkable opportunities tailor for production high-value products. In this discussion, we will briefly examine structural mechanism nitrilase. An overview protein strategies preference, regioselectivity stereoselectivity explored combined with some representative examples recently terms specificity enzyme. The future research trends field also prospected.

Language: Английский

Citations

2
Halloysite Clay Nanotubes for Catalytic Conversion of Biomass: Synergy between Computational Modeling and Experimental Studies DOI
Lorenzo Lisuzzo,

Ludovico Guercio,

Giuseppe Cavallaro

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 18167 - 18203

Published: Nov. 24, 2024

Halloysite clay nanotubes (HNTs) are emerging nanomaterials for numerous environmental applications, including catalysis and biomass valorization. The efficacy of halloysite as a nanoplatform the catalytic conversion can be accurately evaluated by combined approaches based on experimental investigations computational modeling. Recently, many efforts have been made to properly describe most peculiar features focusing its structural interfacial through studies, which challenging natural nanoparticles yet crucial design novel catalysts exploited in conversion. Within this framework, review critically extensively discusses recent advancements related use different processes, such enzymatic reactions, precious- nonprecious-metal- alloy-catalyzed acid-activated mechanisms. research gap modeling chemical occurring surfaces is highlighted throughout review, together with latest achievements. To optimize efficiency halloysite-based materials valorization, future should focus implementation data calculations provided proper models synergistic approach.

Language: Английский

Citations

5
Enhanced synthesis of chloramphenicol intermediate L-threo-p-nitrophenylserine using engineered L-threonine transaldolase and by-product elimination DOI
Zhiwen Xi,

Yan Xu,

Zhiyong Liu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 263, P. 130310 - 130310

Published: Feb. 20, 2024

Language: Английский

Citations

3
Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene‑Hopene Cyclases DOI Creative Commons
Julian Ludwig, Christian Curado‐Carballada, Stephan C. Hammer

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 25, 2024

Abstract The interconversion of monoterpenes is facilitated by a complex network carbocation rearrangement pathways. Controlling these isomerization pathways challenging when using common Brønsted and Lewis acid catalysts, which often produce product mixtures that are difficult to separate. In contrast, natural monoterpene cyclases exhibit high control over the reactions but reliant on phosphorylated substrates. this study, we present engineered squalene‐hopene from Alicyclobacillus acidocaldarius ( Aac SHC) catalyze with unprecedented precision. Starting promiscuous (+)‐β‐pinene, first demonstrate noticeable shifts in distribution solely introducing single point mutations. Furthermore, showcase tuneable cation steering enhancing (+)‐borneol selectivity 1 % >90 (>99 de ) aided iterative saturation mutagenesis. Our combined experimental computational data suggest reorganization key aromatic residues leads restructuring water facilitates selective termination secondary isobornyl cation. This work expands our mechanistic understanding rearrangements sets stage for target‐oriented skeletal broadly abundant terpenes.

Language: Английский

Citations

2
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
Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene‑Hopene Cyclases DOI Creative Commons
Julian Ludwig, Christian Curado‐Carballada, Stephan C. Hammer

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 25, 2024

Abstract The interconversion of monoterpenes is facilitated by a complex network carbocation rearrangement pathways. Controlling these isomerization pathways challenging when using common Brønsted and Lewis acid catalysts, which often produce product mixtures that are difficult to separate. In contrast, natural monoterpene cyclases exhibit high control over the reactions but reliant on phosphorylated substrates. this study, we present engineered squalene‐hopene from Alicyclobacillus acidocaldarius ( Aac SHC) catalyze with unprecedented precision. Starting promiscuous (+)‐β‐pinene, first demonstrate noticeable shifts in distribution solely introducing single point mutations. Furthermore, showcase tuneable cation steering enhancing (+)‐borneol selectivity 1 % >90 (>99 de ) aided iterative saturation mutagenesis. Our combined experimental computational data suggest reorganization key aromatic residues leads restructuring water facilitates selective termination secondary isobornyl cation. This work expands our mechanistic understanding rearrangements sets stage for target‐oriented skeletal broadly abundant terpenes.

Language: Английский

Citations

0
A Career in Catalysis: Bernhard Hauer DOI
Bernd A. Nebel, Michael Breuer, Andreas Schneider

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 8861 - 8889

Published: June 20, 2023

On the occasion of Professor Bernhard Hauer′s (partial) retirement, we reflect on and highlight his distinguished career in biocatalysis. Bernhard, a biologist by training, has greatly influenced biocatalysis with vision ideas throughout four-decade career. The development went hand evolution application enzymes for chemical processes. In this Account, present selected examples early work their an industrial setting, focus specific contributions to harnessing catalytic power novel reactions understanding engineering flexible loops channels catalysis.

Language: Английский

Citations

1
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