Discovery of Noncanonical Iron and 2-Oxoglutarate Dependent Enzymes Involved in C–C and C–N Bond Formation in Biosynthetic Pathways DOI Creative Commons
Yaoyao Shen, Aimin Sun, Yisong Guo

et al.

ACS Bio & Med Chem Au, Journal Year: 2025, Volume and Issue: 5(2), P. 238 - 261

Published: March 10, 2025

Iron and 2-oxoglutarate dependent (Fe/2OG) enzymes utilize an FeIV═O species to catalyze the functionalization of otherwise chemically inert C–H bonds. In addition more familiar canonical reactions hydroxylation chlorination, they also several other types that contribute diversity complexity natural products. past decade, new Fe/2OG C–C C–N bond formation have been reported in biosynthesis structurally complex Compared with catalytic cycles these involve distinct mechanistic features enable noncanonical reaction outcomes. This Review summarizes recent discoveries involved a focus on mechanisms their roles product biosynthesis.

Language: Английский

Diverging Reaction Pathways and Key Intermediates in Ethylene Forming Enzyme DOI
Chao Wang, Elvira R. Sayfutyarova

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Ethylene-forming enzyme (EFE) is a non-heme iron(II)- and 2-oxoglutarate-(Fe(II)/2OG)-dependent oxygenase with distinct catalytic reactivity. While most Fe(II)/2OG-dependent oxygenases catalyze substrate hydroxylation the 2OG decarboxylation to succinate, EFE primarily converts into CO2 ethylene. In this work, we employ multifaceted approach, including molecular dynamics, quantum mechanics methods, theoretical Mössbauer spectroscopy, analysis of intrinsic electric field exerted by protein environment, examine possible reaction pathways. Our study reveals novel second branch point, where ethylene formation (EF) 3-hydroxypropionate pathways diverge following Fe(III)-carbonate C3-C5-derived propion-3-yl radical intermediates, occurring earlier than suggested in previous studies. We identified multiple subsequent EF characterized low-energy barrier either Fe(II)-carbonates or Fe(II)-pyrocarbonates. Based on these findings, introduce revised mechanism for EFE, which consistent available experimental data highlights importance retaining C2-derived CO2, generated stages, within active site pathway. also intermediates that can produce quadrupole doublet peak observed recent experiments associated unidentified Fe(II)-containing species characteristic ethylene-forming This work provides new insights both first branchpoints pathway be useful modifications aimed at shifting product yield reaction.

Language: Английский

Citations

0
Discovery of Noncanonical Iron and 2-Oxoglutarate Dependent Enzymes Involved in C–C and C–N Bond Formation in Biosynthetic Pathways DOI Creative Commons
Yaoyao Shen, Aimin Sun, Yisong Guo

et al.

ACS Bio & Med Chem Au, Journal Year: 2025, Volume and Issue: 5(2), P. 238 - 261

Published: March 10, 2025

Iron and 2-oxoglutarate dependent (Fe/2OG) enzymes utilize an FeIV═O species to catalyze the functionalization of otherwise chemically inert C–H bonds. In addition more familiar canonical reactions hydroxylation chlorination, they also several other types that contribute diversity complexity natural products. past decade, new Fe/2OG C–C C–N bond formation have been reported in biosynthesis structurally complex Compared with catalytic cycles these involve distinct mechanistic features enable noncanonical reaction outcomes. This Review summarizes recent discoveries involved a focus on mechanisms their roles product biosynthesis.

Language: Английский

Citations

0