A5086858429- Metal-Catalyzed Oxygenation Mechanisms
- Photosynthetic Processes and Mechanisms
- Metal complexes synthesis and properties
- Microbial bioremediation and biosurfactants
- Metalloenzymes and iron-sulfur proteins
- Porphyrin Metabolism and Disorders
- Gut microbiota and health
- Folate and B Vitamins Research
- Microbial Metabolic Engineering and Bioproduction
- Biochemical and Molecular Research
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Porphyrin and Phthalocyanine Chemistry
- Chemical Synthesis and Characterization
- Pesticide and Herbicide Environmental Studies
- Oxidative Organic Chemistry Reactions
- Diet and metabolism studies
- Electrocatalysts for Energy Conversion
- Enzyme-mediated dye degradation
- Biofuel production and bioconversion
- Metabolomics and Mass Spectrometry Studies
- Hemoglobin structure and function
- Photodynamic Therapy Research Studies
- Cancer, Hypoxia, and Metabolism
- Metal-Organic Frameworks: Synthesis and Applications
University of Washington
2023-2024
Seattle University
2024
Harvard University
2018-2021
Pennsylvania State University
2013-2020
Harvard University Press
2018-2019
Wake Forest University
2012
Hydroxylation of aliphatic carbons by nonheme Fe(IV)-oxo (ferryl) complexes proceeds hydrogen-atom (H•) transfer (HAT) to the ferryl and subsequent coupling between carbon radical Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H•-abstracting for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C–C desaturations, it has been proposed a second HAT Fe(III)–OH complex from α preempts rebound. Deuterium (2H) at...
Cyanobacterial aldehyde-deformylating oxygenases (ADOs) belong to the ferritin-like diiron-carboxylate superfamily of dioxygen-activating proteins. They catalyze conversion saturated or monounsaturated C(n) fatty aldehydes formate and corresponding C(n-1) alkanes alkenes, respectively. This unusual, apparently redox-neutral transformation actually requires four electrons per turnover reduce O2 cosubstrate oxidation state water incorporates one O-atom from into coproduct. We show here that...
Aldehyde-deformylating oxygenase (ADO) is a ferritin-like nonheme-diiron enzyme that catalyzes the last step in pathway through which fatty acids are converted into hydrocarbons cyanobacteria. ADO conversion of aldehyde to corresponding alk(a/e)ne and formate, consuming four electrons one molecule O2 per turnover incorporating atom from formate coproduct. The source reducing equivalents vivo has not been definitively established, but cyanobacterial [2Fe-2S] ferredoxin (PetF), reduced by...
The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 of dodecanoic acid to produce 1-undecene CO2. A published X-ray crystal structure showed that has a heme-oxygenase-like fold, thus associating it with structural superfamily includes known postulated non-heme diiron proteins, but revealed only single iron ion in active site. Mechanisms proposed for initiation decarboxylation by cleavage using monoiron cofactor activate O2 necessarily invoked unusual or potentially unfeasible...
Trimethylamine (TMA) is an important gut microbial metabolite strongly associated with human disease. There are prominent gaps in our understanding of how TMA produced from the essential dietary nutrient l-carnitine, particularly anoxic environment where oxygen-dependent l-carnitine-metabolizing enzymes likely inactive. Here, we elucidate chemical and genetic basis for anaerobic generation l-carnitine-derived γ-butyrobetaine (γbb) by bacterium Emergencia timonensis We identify a set genes...
Hydrogen-atom transfer (HAT) from a substrate carbon to an iron(IV)-oxo (ferryl) intermediate initiates diverse array of enzymatic transformations. For outcomes other than hydroxylation, coupling the resultant radical and hydroxo ligand (oxygen rebound) must generally be averted. A recent study FtmOx1, fungal iron(II)- 2-(oxo)glutarate-dependent oxygenase that installs endoperoxide verruculogen by adding O2 between carbons 21 27 fumitremorgin B, posited tyrosine (Tyr or Y) 224 serves as HAT...
A two-step pathway consisting of an acyl-acyl carrier protein (ACP) reductase (AAR) and aldehyde-deformylating oxygenase (ADO) allows various cyanobacteria to convert long-chain fatty acids into hydrocarbons. AAR catalyzes the two-electron, NADPH-dependent reduction a acid attached ACP via thioester linkage corresponding aldehyde, while ADO transforms aldehyde Cn-1 hydrocarbon C1-derived formate. Considering that heptadec(a/e)ne is most prevalent produced by cyanobacterial ADOs, insolubility...
A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae ( Fj) differs fundamentally known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O2-) activation, but it does not require O2--supplying flavoprotein (NrdI) needed in systems, instead scavenging oxidant solution. Although Fj has tyrosine at appropriate sequence position (Tyr 104), this residue is oxidized...
ABSTRACT ThiI has been identified as an essential enzyme involved in the biosynthesis of thiamine and tRNA thionucleoside modification, 4-thiouridine. In Escherichia coli Salmonella enterica , acts a sulfurtransferase, receiving sulfur donated from cysteine desulfurase IscS transferring it to target molecule or additional carrier proteins. However, Bacillus subtilis most species Firmicutes phylum, lacks rhodanese domain that contains site responsible for sulfurtransferase activity. The lack...
Activation of O-H bonds by inorganic metal-oxo complexes has been documented, but no cognate enzymatic process is known. Our mechanistic analysis 2-hydroxyethylphosphonate dioxygenase (HEPD), which cleaves the C1-C2 bond its substrate to afford hydroxymethylphosphonate on biosynthetic pathway commercial herbicide phosphinothricin, uncovered an example such O-H-bond-cleavage event. Stopped-flow UV-visible absorption and freeze-quench Mössbauer experiments identified a transient iron(IV)-oxo...
The assignment of biochemical functions to hypothetical proteins is challenged by functional diversification within many protein structural superfamilies. This diversification, which particularly common for metalloenzymes, renders annotations that are founded solely on sequence and domain similarities unreliable often erroneous. Definitive characterization delineate subgroups these superfamilies will aid in improving bioinformatic approaches annotation. We describe here the two non-heme-iron...
The synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) is an active ingredient of thousands commercial herbicides. Multiple species bacteria degrade 2,4-D via a pathway initiated by the Fe(II) and α-ketoglutarate (Fe/αKG)-dependent aryloxyalkanoate dioxygenases (AADs). Recently, genes encoding 2 AADs have been deployed commercially in herbicide-tolerant crops. Some can also inactivate chiral phenoxypropionate aryloxyphenoxypropionate (AOPP) herbicides, albeit with varying substrate...
The class A flavoenzyme 6-hydroxynicotinate 3-monooxygenase (NicC) catalyzes a rare decarboxylative hydroxylation reaction in the degradation of nicotinate by aerobic bacteria. While structure and critical residues involved catalysis have been reported, mechanism this multistep enzyme has yet to be determined. kinetic understanding NicC would enable comparison other phenolic hydroxylases illuminate its bioengineering potential for remediation N-heterocyclic aromatic compounds. Toward these...
ABSTRACT Trimethylamine (TMA) is an important gut microbial metabolite strongly associated with human disease. There are prominent gaps in our understanding of how TMA produced from the essential dietary nutrient L-carnitine, particularly anoxic environment where oxygen-dependent L-carnitine-metabolizing enzymes likely inactive. Here, we elucidate chemical and genetic basis for anaerobic generation L-carnitine-derived γ-butyrobetaine (γbb) by bacterium Emergencia timonensis . We identify a...
Cyanobacteria utilize sunlight to fix carbon dioxide form biomolecules such as fatty acids. These microbes can convert acids into diesel fuel hydrocarbons via a two‐enzyme pathway, which has been targeted for application in renewable bioprocesses. The first enzyme, acyl‐acyl carrier protein reductase (AAR), catalyzes two‐electron, NADPH‐dependent reduction of its C n ‐fatty acyl‐ACP substrate yield aldehyde. This reaction provides the second aldehyde‐deformylating oxygenase (ADO),...