Debottlenecking cytochrome P450-dependent metabolic pathways for the biosynthesis of commercial natural products DOI
Susanne M. Germann, M Holtz, Michael K. Jensen

et al.

Natural Product Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Covering: 2016 to the end of 2024This highlight article aims provide a perspective on challenges that novel biotechnological processes face in biomanufacturing natural products (NPs) whose biosynthesis pathways rely cytochrome P450 monooxygenases. This enzyme superfamily is one most versatile plethora NPs finding use across food, nutrition, medicine, chemical and cosmetics industries. These enzymes often exhibit excellent regio- stereoselectivity, but they can suffer from low activity instability, which are serious issues impairing development high performing bioprocesses. We start with brief introduction industrial biotechnology importance looking for alternative means producing independently unsustainable fossil fuels or plant extractions. then discuss implemented solutions during commercial NP focusing P450-dependent steps primarily yeast cell factories. Our main focus encountered when utilizing pathways, how protein engineering be used debottlenecking them. Finally, we briefly touch upon artificial intelligence machine learning guiding efforts.

Language: Английский

Quantum Mechanical Cluster Models for Calculations on Enzymatic Reaction Mechanisms: Set‐Up and Accuracy DOI Creative Commons
Sam P. de Visser, Henrik P. H. Wong, Yi Zhang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(60)

Published: Aug. 7, 2024

Enzymes turnover substrates into products with amazing efficiency and selectivity as such have great potential for use in biotechnology pharmaceutical applications. However, details of their catalytic cycles the origins surrounding regio- chemoselectivity enzymatic reaction processes remain unknown, which makes engineering enzymes challenging. Computational modelling can assist experimental work field establish factors that influence rates product distributions. A popular approach is quantum mechanical cluster models take first- second coordination sphere enzyme active site consideration. These QM are widely applied but often results obtained dependent on model choice selection. Herein, we show give highly accurate reproduce distributions free energies activation within several kcal mol

Language: Английский

Citations

7
Computational Advances in Ionic Liquid Applications for Green Chemistry: A Critical Review of Lignin Processing and Machine Learning Approaches DOI Creative Commons
Brian Taylor, Nikhil Kumar, Dhirendra Kumar Mishra

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(21), P. 5073 - 5073

Published: Oct. 26, 2024

The valorization and dissolution of lignin using ionic liquids (ILs) is critical for developing sustainable biorefineries a circular bioeconomy. This review aims to critically assess the current state computational machine learning methods understanding optimizing IL-based processes reported since 2022. paper examines various approaches, from quantum chemistry learning, highlighting their strengths, limitations, recent advances in predicting lignin-IL interactions. Key themes include challenges accurately modeling lignin’s complex structure, development efficient screening methodologies enhance processes, integration with calculations. These will drive progress by providing deeper molecular-level insights facilitating rapid novel IL-lignin systems.

Language: Английский

Citations

4
Computational Modeling of the Enzymatic Achmatowicz Rearrangement by Heme-Dependent Chloroperoxidase: Reaction Mechanism, Enantiopreference, Regioselectivity, and Substrate Specificity DOI
Fuqiang Chen, Chenghua Zhang, Shiqing Zhang

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

The chloroperoxidase from Caldariomyces fumago (CfCPO) catalyzes the oxidative ring expansion of α-heterofunctionalized furans via Achmatowicz rearrangement, providing an elegant tool to convert furan rings into complex-prefunctionalized scaffolds. However, mechanism this transformation remains unclear. Herein, CfCPO-catalyzed reaction rac-1-(2-furyl)ethanol (1a) is studied by quantum chemical calculations and molecular dynamics simulations. reveal that conversion follows general reaction. Notably, binding 1a enzyme's active site influences Compound I (Cpd I) formation, (R)-1a enantiomer results in a lower barrier compared (S)-1a, explaining observed (R)-enantiopreference toward racemic substrate. Additionally, due weaker steric hindrance between porphyrin substrate, nucleophilic attack Cpd on core preferred at less-substituted C4=C5 bond, rationale for experimentally regioselectivity. Finally, bottleneck residues substrate delivery channel also surroundings are proposed be responsible specificity CfCPO. This study lays theoretical foundation rational design new CPOs catalyze rearrangement with broader spectrum or specific stereopreference.

Language: Английский

Citations

0
Mechanistic Insights into CYP199A4-Catalyzed α-Hydroxyketone Formation and Hydrogen Bond-Assisted C–C Bond Cleavage Catalyzed by the CYP199A4 F182L Mutant DOI Open Access
Chang Yuan, Jiaqi Xu, Shun Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1526 - 1526

Published: Feb. 11, 2025

CYP199A4 is a cytochrome P450 and can catalyze the hydroxylation of 4-propionylbenzoic acid (4-pIBA) to generate α-hydroxyketone with high stereoselectivity. The F182L mutant (F182L-CYP199A4) has been shown support cleavage C-C bond between carbonyl hydroxyl groups α-hydroxyketone, whereas wild-type cannot. To uncover how Phe182 regulates substrate reactivity, we conducted classical molecular dynamics (MD) quantum mechanics/molecular mechanics (QM/MM) MD simulations on these systems. results predicted that formation preferentially led (S)-enantiomer. Moreover, findings revealed F182L-CYP199A4 facilitated hydrogen reactive peroxoanion (POA) species. This interaction stabilized near POA promoted subsequent cleavage. mechanism were elucidated by employing hybrid density functional theory (DFT). involved C-H 4-pIBA rate-limiting energy barrier 17.1 kcal/mol. catalyzed occurred via radical attack mechanism.

Language: Английский

Citations

0
Lignin: An Adaptable Biodegradable Polymer Used in Different Formulation Processes DOI Creative Commons
Andreea Crețeanu, Claudiu N. Lungu,

Mirela Lungu

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1406 - 1406

Published: Oct. 21, 2024

LIG is a biopolymer found in vascular plant cell walls that created by networks of hydroxylated and methoxylated phenylpropane are randomly crosslinked. Plant contain LIG, with significant potential for usage modern industrial pharmaceutical applications. It renewable raw resource. The mechanically protected this substance, which may increase its durability. Because it has antibacterial antioxidant qualities, also shields plants from biological chemical challenges the outside world. Researchers have done great deal work to create new materials substances based on LIG. Numerous applications, including those involving agents, additives, UV protection hydrogel-forming molecules, nanoparticles, solid dosage forms, been made biopolymer.

Language: Английский

Citations

2
Debottlenecking cytochrome P450-dependent metabolic pathways for the biosynthesis of commercial natural products DOI
Susanne M. Germann, M Holtz, Michael K. Jensen

et al.

Natural Product Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Covering: 2016 to the end of 2024This highlight article aims provide a perspective on challenges that novel biotechnological processes face in biomanufacturing natural products (NPs) whose biosynthesis pathways rely cytochrome P450 monooxygenases. This enzyme superfamily is one most versatile plethora NPs finding use across food, nutrition, medicine, chemical and cosmetics industries. These enzymes often exhibit excellent regio- stereoselectivity, but they can suffer from low activity instability, which are serious issues impairing development high performing bioprocesses. We start with brief introduction industrial biotechnology importance looking for alternative means producing independently unsustainable fossil fuels or plant extractions. then discuss implemented solutions during commercial NP focusing P450-dependent steps primarily yeast cell factories. Our main focus encountered when utilizing pathways, how protein engineering be used debottlenecking them. Finally, we briefly touch upon artificial intelligence machine learning guiding efforts.

Language: Английский

Citations

0