A5087876784- Bacterial Genetics and Biotechnology
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Marine Sponges and Natural Products
- Peptidase Inhibition and Analysis
- Chemical synthesis and alkaloids
- Biochemical and Structural Characterization
- Vibrio bacteria research studies
- RNA regulation and disease
- Traditional and Medicinal Uses of Annonaceae
- RNA Research and Splicing
- Microbial Metabolites in Food Biotechnology
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Antimicrobial Resistance in Staphylococcus
- Enzyme Structure and Function
- Alkaloids: synthesis and pharmacology
- Enzyme Production and Characterization
- Phytochemistry and Bioactive Compounds
- Hemoglobin structure and function
- Bacterial biofilms and quorum sensing
- Pneumonia and Respiratory Infections
- Carbohydrate Chemistry and Synthesis
Brigham and Women's Hospital
2020-2024
Harvard University
2015-2024
Chulalongkorn University
2023-2024
Howard Hughes Medical Institute
2020-2022
Harvey Mudd College
2015
Cell elongation in rod-shaped bacteria is mediated by the Rod system, a conserved morphogenic complex that spatially controls cell wall assembly glycan polymerase RodA and crosslinking enzyme PBP2. Using Escherichia coli as model we identified PBP2 variant promotes system function when essential accessory components of machinery are inactivated. This hyperactivates synthesis vivo stimulates activity RodA-PBP2 complexes vitro. Cells with activated synthase also exhibited enhanced...
The microbial cell wall is essential for maintenance of shape and resistance to external stressors1. primary structural component the peptidoglycan, a glycopolymer with peptide crosslinks located outside membrane1. Peptidoglycan biosynthesis structure are responsive shifting environmental conditions such as pH salinity2-6, but mechanisms underlying adaptations incompletely understood. Precursors peptidoglycan other surface glycopolymers synthesized in cytoplasm then delivered across membrane...
Lysobactin, also known as katanosin B, is a potent antibiotic with in vivo efficacy against Staphylococcus aureus and Streptococcus pneumoniae. It was previously shown to inhibit peptidoglycan (PG) biosynthesis, but its molecular mechanism of action has not been established. Using enzyme inhibition assays, we show that lysobactin forms 1:1 complexes Lipid I, II, II(A)(WTA), substrates the PG wall teichoic acid (WTA) biosynthetic pathways. Therefore, lysobactin, like ramoplanin teixobactin,...
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global public health problem. MRSA strains have acquired non-native penicillin-binding protein called PBP2a that cross-links peptidoglycan when the native S. PBPs inhibited by β-lactams. It has been proposed can use cell wall precursors having different glycine branch lengths (penta-, tri-, or monoglycine), while only cross-link strands bearing complete pentaglycine branch. This hypothesis never tested because necessary...
Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ Vibrio cholerae tRNA. Here, we characterize the biogenesis, regulation, and functions of this previously undescribed process. show that an enzyme, TrcP, mediates C-to-U followed by conversion U to Ψ, consecutively. AlphaFold-2 predicts TrcP consists two globular domains (cytidine deaminase pseudouridylase) long helical domain. The latter domain tethers tRNA substrates...
A green organic–inorganic laboratory experiment has been developed in which students prepare a self-assembling iron cage D2O at room temperature. The tetrahedral captures small, neutral molecule such as cyclohexane or tetrahydrofuran. 1H NMR analysis distinguishes captured and free guests through diagnostic chemical shifts, splitting patterns, diffusion coefficients (using DOSY), the appearance of hydrophobic molecules even when are insoluble water. Students invited to test their hypotheses...
In a looming post-antibiotic era, antibiotic alternatives have become key players in the combat against pathogens. Although recent advances genomic research allow scientists to fully explore an organism's genome search for novel antibacterial molecules, laborious work is still needed order dissect each individual gene product its activity. Here, we exploited phage-induced bacterial morphological changes as anchors and discover potential phage-derived antimicrobial embedded phage genome. We...
We present a four-step synthesis of (+)-artemone from (–)-linalool, featuring iminium organocatalysis doubly diastereoselective conjugate addition reaction. The strategy follows proposed biosynthetic pathway, rapidly generates stereochemical complexity, uses no protecting groups, and minimizes redox manipulations.
ABSTRACT Cell elongation in rod-shaped bacteria is mediated by the Rod system, a conserved morphogenic complex that spatially controls cell wall (CW) assembly. In Escherichia coli , alterations CW synthase component of system called PBP2 were identified overcome other inactivating defects. activity was stimulated suppressors vivo, and purified complexes with these changes showed more robust synthesis vitro. Polymerization actin-like MreB also found to be enhanced cells activated synthase....
Abstract The mechanisms that enable adaptation of peptidoglycan, the structural unit bacterial cell wall, to shifting extracellular conditions such as pH remain largely unknown. Here, we identify a DUF368-containing membrane protein in cholera pathogen Vibrio cholerae is critical for pathogenesis and alkaline fitness. V. Staphylococcus aureus lacking their cognate have pH-dependent wall defects consistent with surface accumulation undecaprenyl phosphate (C55-P), an essential lipid carrier...
Summary Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ Vibrio cholerae tRNA. Here, we characterize the biogenesis, regulation, and functions of this previously undescribed process. show that an enzyme, TrcP, mediates C-to-U followed by conversion U to Ψ, consecutively. AlphaFold-2 predicts TrcP consists two globular domains, including novel cytidine deaminase pseudouridylase, along with long helical domain. The...