A5019238818- Metal-Catalyzed Oxygenation Mechanisms
- Photosynthetic Processes and Mechanisms
- Metalloenzymes and iron-sulfur proteins
- Microbial Natural Products and Biosynthesis
- Computational Drug Discovery Methods
- Plant Pathogens and Fungal Diseases
- Porphyrin and Phthalocyanine Chemistry
- Plant-Microbe Interactions and Immunity
- Carbohydrate Chemistry and Synthesis
- Pharmacogenetics and Drug Metabolism
- Microbial Metabolic Engineering and Bioproduction
- Plant Pathogens and Resistance
- Synthesis and Catalytic Reactions
- Porphyrin Metabolism and Disorders
- Microbial metabolism and enzyme function
- Enzyme Catalysis and Immobilization
- Redox biology and oxidative stress
- Plant biochemistry and biosynthesis
- Metal complexes synthesis and properties
- CO2 Reduction Techniques and Catalysts
- Catalytic C–H Functionalization Methods
University of California, Berkeley
2016-2023
Lawrence Berkeley National Laboratory
2009-2023
Massachusetts Institute of Technology
2003-2004
IIT@MIT
2003
Production of fine chemicals from heterologous pathways in microbial hosts is frequently hindered by insufficient knowledge the native metabolic pathway and its cognate enzymes; often unresolved, enzymes lack detailed characterization. An alternative paradigm to using de novo design well-characterized, substrate-promiscuous enzymes. We demonstrate this concept P450(BM3) Bacillus megaterium. Using a computer model, we illustrate how key active site mutations enable binding non-native...
Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. The enzyme is composed two subunits: R1 and R2. contains active site for nucleotide reduction allosteric effector sites that regulate specificity turnover rate. R2 diferric-tyrosyl (Y•) radical cofactor initiates by a putative long-range proton-coupled electron transfer (PCET) pathway over 35 Å. This thought involve specific amino acid intermediates (Y122 W48...
Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms, providing monomeric precursors required for DNA replication and repair. The class I RNRs are composed two subunits; R1 subunit contains active site nucleotide reduction allosteric effector binding sites, whereas R2 houses essential diirontyrosyl (Y·) radical cofactor. A major unresolved issue is mechanism by which tyrosyl on (Y122, Escherichia coli numbering) reversibly generates...
Abstract For see ChemInform in Full Text.
An aliphatic halogenase requires four substrates: 2-oxoglutarate (2OG), halide (Cl - or Br ), the halogenation target ("prime substrate"), and dioxygen. In well-studied cases, three non-gaseous substrates must bind to activate enzyme's Fe(II) cofactor for efficient capture of O 2 . Halide, 2OG, (lastly) all coordinate directly initiate its conversion a cis -halo-oxo-iron(IV) (haloferryl) complex, which abstracts hydrogen (H•) from non-coordinating prime substrate enable radicaloid...
Abstract The activation of inert C( sp 3 )-H bonds by non-heme Fe enzymes plays a key role in metabolism, epigenetics, and signaling, while providing powerful biocatalytic platform for the chemical synthesis molecules with increased complexity. In this context, II /α-ketoglutarate-dependent radical halogenases represent broadly interesting system, as they are uniquely capable carrying out transfer diverse array bound anions following C-H activation. Here, we provide first experimental...
Abstract Amino acids (AAs) are modular and modifiable building blocks which nature uses to synthesize both macromolecules, such as proteins, small molecule natural products, alkaloids non-ribosomal peptides (NRPs). While the 20 main proteinogenic AAs display relatively limited side-chain diversity, a wide range of non-canonical amino (ncAAs) exist that not used by ribosome for protein synthesis but contain broad array structural features functional groups found in AAs. In this communication,...
ABSTRACT Biocatalytic C–H activation has the potential to merge enzymatic and synthetic strategies for bond formation. Fe II /αKG-dependent halogenases are particularly distinguished their ability both control selective C-H as well direct group transfer of a bound anion along reaction axis separate from oxygen rebound, enabling development new transformations. In this context, we elucidate basis selectivity enzymes that perform halogenation yield 4-Cl-lysine (BesD), 5-Cl-lysine (HalB),...