Year: 2024
Type: article
Abstract: Single component flavin-dependent halogenases (FDHs) possess both flavin reductase and FDH activity in a single enzyme. We recently reported that the single component FDH AetF catalyzes site-selective bromination and iodination of a variety of aromatic substrates and enantioselective bromolactonization and iodoetherification of styrenes bearing pendant carboxylic acid or alcohol substituents. Given this inherent reactivity and selectivity, we explored the utility of AetF as catalyst for alkene and alkyne C-H halogenation. We find that AetF catalyzes halogenation of a range of 1,1-disubstituted styrenes, often with high stereoselectivity. Despite the utility of haloalkenes for cross-coupling and other applications, accessing these compounds in a stereoselective manner typically requires functional group interconversion processes, and selective halogenation of 1,1'-disubstituted olefins remains rare. We also establish that AetF and homologues of this enzyme can halogenate terminal alkynes. Mutagenesis studies and deuterium kinetic isotope effects are used to support a mechanistic proposal involving covalent catalysis for halogenation of unactivated alkynes by AetF homologues. These findings expand the scope of FDH catalysis and continue to show the unique utility of single component FDHs for biocatalysis.
Institutions: Indiana University Bloomington, Indiana University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
Awards: G1042813737, Engineering Halogenases for Small Molecule Functionalization and Enantioselective Catalysis, Heirarchical Modeling of Incompressible Turbulent Flows Using Divergence-Free Vector Wavelets, G415980670, G4412226944, G5028622094, MRI: Acquisition of a High Resolution GC-MS-MS with Fully Automated Sample Preparation to Advance Chemical Synthesis, Metabolomics, and Geochemical Research at IU Bloomington, MRI: Acquisition of a 500 MHz State-of-the-Art Nuclear Magnetic Resonance (NMR)Spectrometer, Directed Evolution of Halogenases for Small Molecule Functionalization
OpenAlex ID: W4391275375