Harder, better, faster, stronger: Large-scale QM and QM/MM for predictive modeling in enzymes and proteins

V Vennelakanti, A Nazemi, R Mehmood… - Current opinion in …, 2022 - Elsevier
Computational prediction of enzyme mechanism and protein function requires accurate
physics-based models and suitable sampling. We discuss recent advances in large-scale …

Recent developments in the total synthesis of natural products using the Ugi multicomponent reactions as the key strategy

EL Larghi, ABJ Bracca, SO Simonetti… - Organic & Biomolecular …, 2024 - pubs.rsc.org
The total syntheses of selected natural products using different versions of the Ugi
multicomponent reaction is reviewed on a case-by-case basis. The revision covers the …

Unusual dioxygen-dependent reactions catalyzed by nonheme iron enzymes in natural product biosynthesis

R Ushimaru, I Abe - ACS Catalysis, 2022 - ACS Publications
Nonheme iron-dependent enzymatic reactions play crucial roles in building and modifying
bioactive organic molecules in all major classes of natural product pathways. While the …

Mechanistic insights into substrate positioning that distinguish non-heme Fe (II)/α-ketoglutarate-dependent halogenases and hydroxylases

DW Kastner, A Nandy, R Mehmood, HJ Kulik - ACS Catalysis, 2023 - ACS Publications
Non-heme iron halogenases and hydroxylases activate inert C–H bonds to selectively
catalyze the functionalization of diverse biological products under physiological conditions …

Optimized Substrate Positioning Enables Switches in the C–H Cleavage Site and Reaction Outcome in the Hydroxylation–Epoxidation Sequence Catalyzed by …

ES Wenger, RJ Martinie, R Ushimaru… - Journal of the …, 2024 - ACS Publications
Hyoscyamine 6β-hydroxylase (H6H) is an iron (II)-and 2-oxoglutarate-dependent (Fe/2OG)
oxygenase that produces the prolifically administered antinausea drug, scopolamine. After …

Biosynthesis of triacsin featuring an N-hydroxytriazene pharmacophore

A Del Rio Flores, FF Twigg, Y Du, W Cai… - Nature chemical …, 2021 - nature.com
Triacsins are an intriguing class of specialized metabolites possessing a conserved N-
hydroxytriazene moiety not found in any other known natural products. Triacsins are notable …

Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis

C Gui, E Kalkreuter, YC Liu, G Li, AD Steele… - Nature Chemical …, 2024 - nature.com
The anthraquinone-fused enediynes (AFEs) combine an anthraquinone moiety and a ten-
membered enediyne core capable of generating a cytotoxic diradical species. AFE …

Repurposing Iron‐and 2‐Oxoglutarate‐Dependent Oxygenases to Catalyze Olefin Hydration

B Wang, Y Lu, L Cha, TY Chen… - Angewandte Chemie …, 2023 - Wiley Online Library
Mononuclear nonheme iron (II) and 2‐oxoglutarate (Fe/2OG)‐dependent oxygenases and
halogenases are known to catalyze a diverse set of oxidative reactions, including …

Deciphering the reaction pathway of mononuclear iron enzyme-catalyzed N≡ C triple bond formation in isocyanide lipopeptide and polyketide biosynthesis

TY Chen, Z Zheng, X Zhang, J Chen, L Cha… - ACS …, 2022 - ACS Publications
Despite the diversity of reactions catalyzed by 2-oxoglutarate-dependent nonheme iron
(Fe/2OG) enzymes identified in recent years, only a limited number of these enzymes have …

Probing the mechanism of isonitrile formation by a non-heme iron (II)-dependent oxidase/decarboxylase

A Del Rio Flores, DW Kastner, Y Du… - Journal of the …, 2022 - ACS Publications
The isonitrile moiety is an electron-rich functionality that decorates various bioactive natural
products isolated from diverse kingdoms of life. Isonitrile biosynthesis was restricted for over …