A5047714338- Microbial Natural Products and Biosynthesis
- Plant-Microbe Interactions and Immunity
- RNA Interference and Gene Delivery
- Metabolomics and Mass Spectrometry Studies
- Biochemical and Structural Characterization
- Plant Pathogenic Bacteria Studies
- Axon Guidance and Neuronal Signaling
- Click Chemistry and Applications
- Plant biochemistry and biosynthesis
- Advanced biosensing and bioanalysis techniques
- Genomics and Phylogenetic Studies
- Legume Nitrogen Fixing Symbiosis
- Chemical Synthesis and Analysis
- Fungal Biology and Applications
- Receptor Mechanisms and Signaling
- Apelin-related biomedical research
- Mycotoxins in Agriculture and Food
- Fungal and yeast genetics research
- Monoclonal and Polyclonal Antibodies Research
- Supramolecular Self-Assembly in Materials
- Polyomavirus and related diseases
- ATP Synthase and ATPases Research
- Antifungal resistance and susceptibility
- Genetics, Aging, and Longevity in Model Organisms
- Microbial Metabolic Engineering and Bioproduction
University of Tennessee at Knoxville
2020-2025
California Institute of Technology
2019-2024
Circle Park
2024
Cornell University
2013-2019
Weatherford College
2019
Ithaca College
2016-2018
SUNY Cortland
2012
Small molecules (SMs) play central roles as virulence factors of pathogenic fungi and bacteria; however, genomic analyses suggest that the majority microbial SMs have remained uncharacterized. Based on microarray analysis followed by comparative metabolomics overexpression/knockout mutants, we identified a tryptophan-derived iron(III)-complex, hexadehydro-astechrome (HAS), major product cryptic has nonribosomal peptide synthetase (NRPS) gene cluster in human pathogen Aspergillus fumigatus....
Thiocillins from Bacillus cereus ATCC 14579 are members of the well-known thiazolyl peptide class natural product antibiotics, biosynthesis which has recently been shown to proceed via post-translational modification ribosomally encoded precursor peptides. It long hypothesized that final step involves a formal [4 + 2] cycloaddition between two dehydroalanines, unique transformation had eluded enzymatic characterization. Here we demonstrate TclM, single enzyme thiocillin biosynthetic pathway,...
Small-molecule signaling is one major mode of communication within the polymicrobial consortium soil and rhizosphere. While microbial secondary metabolite (SM) production responses individual species have been studied extensively, little known about potentially conserved roles SM signals in multilayered symbiotic or antagonistic relationships. Here, we characterize SM-mediated interaction between plant-pathogenic bacterium Ralstonia solanacearum two fungi Fusarium fujikuroi Botrytis cinerea...
ABSTRACT Microbial secondary metabolites, including isocyanide moieties, have been extensively mined for their repertoire of bioactive properties. Although the first naturally occurring (xanthocillin) was isolated from fungus Penicillium notatum over half a century ago, biosynthetic origins fungal isocyanides remain unknown. Here we report identification family synthases (ICSs) opportunistic human pathogen Aspergillus fumigatus . Comparative metabolomics overexpression or knockout mutants...
Iron plays a critical role in survival and virulence of the opportunistic pathogen Aspergillus fumigatus. Two transcription factors, GATA-factor SreA bZip-factor HapX oppositely monitor iron homeostasis with activating acquisition pathways (e.g., siderophores) shutting down consumptive (and SreA) during starvation conditions whereas negatively regulates corresponding sufficiency. Recently non-ribosomal peptide, hexadehydroastechrome (HAS; tryptophan-derived (III)-complex), has been found...
As microbial genome sequencing becomes more widespread, the capacity of microorganisms to produce an immense number metabolites has come into better view. Utilizing a metabolite/gene cluster correlation platform, biosynthetic origins new family natural products, rimosamides, were discovered. The rimosamides identified in Streptomyces rimosus and associated with their NRPS/PKS-type gene based upon high frequency co-occurrence across 179 strains actinobacteria. This also led discovery related...
The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. can be found in different self-assembly states: as a monomer, dimer, and oligomer. However, we have poor understanding regarding which state is responsible for driving pro-metastatic signaling. To address this limitation, developed SiMPull-POP, single-molecule method accurate quantification of membrane protein self-assembly. Our experiments reveal that reduction plasma cholesterol strongly promotes...
Bacterial–fungal interactions are presumed to be mediated chiefly by small-molecule signals; however, little is known about the signaling networks that regulate antagonistic relationships between pathogens. Here, we show ralstonins, lipopeptides produced plant pathogenic bacteria Ralstonia solanacearum, interfere with germination of plant-pathogenic fungus Aspergillus flavus down-regulating expression a cryptic biosynthetic gene cluster (BGC), named imq. Comparative metabolomic analysis...
Abstract Cyclization of linear dipeptidyl precursors derived from nonribosomal peptide synthetases (NRPSs) into 2,5‐diketopiperazines (DKPs) is a crucial step in the biosynthesis large number bioactive natural products. However, mechanism DKP formation fungi has remained unclear, despite extensive studies their biosyntheses. Here we show that en route to fungal virulence factor gliotoxin requires seemingly extraneous couplet condensation (C) and thiolation (T) domains NRPS GliP. In vivo...
Significance Bacterial pathogens cause plant diseases that threaten the global food supply. To control diseases, it is important to understand how pathogenic bacteria evade defense and promote infection. We identify from phytopathogen Pseudomonas syringae a small-molecule virulence factor—phevamine A. Both chemical structure mode of action phevamine A are different known bacterial phytotoxins. Phevamine promotes growth by suppressing immune responses, including both early (the generation...
Aspergillus fumigatus is an opportunistic human pathogenic fungus causing life-threatening infections in immunocompromised patients. Adaptation to different habitats and also virulence of the depends on signal perception transduction by modules such as cyclic AMP-dependent protein kinase A (PKA) pathway. Here, transcriptome analysis, 632 differentially regulated genes this important signaling cascade were identified, including 23 putative transcriptional regulators. The highest upregulated...
Untargeted metabolomics indicates that the number of unidentified small-molecule metabolites may exceed protein-coding genes for many organisms, including humans, by orders magnitude. Uncovering underlying metabolic networks is essential elucidating physiological and ecological significance these biogenic small molecules. Here we develop a click-chemistry-based enrichment strategy, DIMEN (deep interrogation metabolism via enrichment), apply to investigate ascarosides, family signaling...
Artificial protein hydrogels are an emerging class of biomaterials with numerous prospective applications in tissue engineering and regenerative medicine. These materials likely to be immunogenic due their frequent incorporation novel amino acid sequence domains, which often serve a functional role within the material itself. We engineered injectable "self" "nonself" artificial hydrogels, were predicted have divergent immune outcomes vivo on basis primary sequence. Following implantation...
Liposomes are effective therapeutic delivery nanocarriers due to their ability encapsulate and enhance the pharmacokinetic properties of a wide range therapeutics. Two primary areas in which improvement is needed for liposomal drug infiltrate cells facilitate derivatization liposome surface. Herein, we report platform incorporating cyclic disulfide lipid (CDL) dual purpose enhancing cell entry functionalizing membrane through thiol-disulfide exchange. In order accomplish this, CDL-1 CDL-2,...
We report boronate-caged guanidine-lipid 1 that activates liposomes for cellular delivery only upon uncaging of this compound by reactive oxygen species (ROS) to produce cationic lipid products. These are designed mimic the exceptional cell properties cell-penetrating peptides (CPPs), while inclusion boronate cage is enhance selectivity such entry will be activated in presence ROS. Boronate hydrogen peroxide was verified mass spectrometry and zeta potential (ZP) measurements. A...
Bacterial isoprenoids are necessary for many biological processes, including maintaining membrane integrity, facilitating intercellular communication, and preventing oxidative damage. All bacterial biosynthesized from two five carbon structural isomers, isopentenyl pyrophosphate (IPP) dimethylallyl (DMAPP), which cell impermeant. Herein, we demonstrate exogenous delivery of IPP DMAPP into Bacillus subtilis by utilizing a self-immolative ester (SIE)-caging approach. We initially evaluated...
The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. can be found in different self-assembly states: as a monomer, dimer, and oligomer. However, our understanding remains limited regarding which state is responsible for driving pro-metastatic signaling. To address this limitation, we have developed SiMPull-POP, single-molecule method accurate quantification of membrane protein self-assembly. Our experiments revealed that reduction plasma cholesterol...
Abstract Cyclization of linear dipeptidyl precursors derived from nonribosomal peptide synthetases (NRPSs) into 2,5‐diketopiperazines (DKPs) is a crucial step in the biosynthesis large number bioactive natural products. However, mechanism DKP formation fungi has remained unclear, despite extensive studies their biosyntheses. Here we show that en route to fungal virulence factor gliotoxin requires seemingly extraneous couplet condensation (C) and thiolation (T) domains NRPS GliP. In vivo...
Abstract Isopentenyl pyrophosphate (IPP) and dimethylallyl (DMAPP) are the central five‐carbon precursors to all terpenes. Despite their significance, exogenous, independent delivery of IPP DMAPP cells is impossible as negatively charged makes these molecules membrane impermeant. Herein, we demonstrate a facile method circumvent this challenge through esterification β‐phosphate with two self‐immolative esters (SIEs) that neutralize yield membrane‐permeant analogs DMAPP. Following cellular...