Year: 2023
Type: article
Abstract: Manganese cofactors activate strong chemical bonds in many essential enzymes. Yet very few manganese-dependent enzymes are known to functionalize ubiquitous carbon-hydrogen (C-H) bonds, and those that catalyze this important reaction display limited intrinsic reactivity. Herein, we report that the 2-aminoisobutyric acid hydroxylase from Rhodococcus wratislaviensis requires manganese to functionalize a C-H bond possessing a bond dissociation enthalpy (BDE) exceeding 100 kcal/mol. Structural and spectroscopic studies of this enzyme reveal a redox-active, heterobimetallic manganese-iron active site that utilizes a manganese ion at the locus for O 2 activation and substrate coordination. Accordingly, this enzyme represents the first documented Mn-dependent monooxygenase in biology. Related proteins are widespread in microorganisms suggesting that many uncharacterized monooxygenases may utilize manganese-containing cofactors to accomplish diverse biological tasks.
DOI: 10.1021/jacs.3c03419
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Awards: G1286251239, G2371548206, G2464961839, G303061748, G3884951186, G4654690619, G5570207115, Spectroscopic Investigations of Metalloenzyme Mechanisms, G6550344761, G7283024673, G7863156295, G8229677252, G8925327636, G9000034938, G9000054807, G9000263589, A Synchrotron Radiation Structural Biology Resource, ALS Efficiently Networking Advanced Beam Line Experiments (ALS-ENABLE), G911061179, G969889393
OpenAlex ID: W4384922738