A5040683433- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Pharmacogenetics and Drug Metabolism
- Genomics and Phylogenetic Studies
- Biochemical and Structural Characterization
- Adipose Tissue and Metabolism
- Fungal Biology and Applications
- Algal biology and biofuel production
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- RNA and protein synthesis mechanisms
- Plant biochemistry and biosynthesis
- Biocrusts and Microbial Ecology
- Phytochemical compounds biological activities
- Catalytic C–H Functionalization Methods
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Synthesis and Analysis
- Antimicrobial Peptides and Activities
- Plant Disease Resistance and Genetics
- Enzyme Catalysis and Immobilization
- Antibiotic Resistance in Bacteria
- Microbial Metabolism and Applications
- X-ray Diffraction in Crystallography
- Coral and Marine Ecosystems Studies
- Cancer Research and Treatments
University of Florida
2016-2025
Florida College
2025
Gainesville Obstetrics & Gynecology
2016-2019
International Drug Development
2017
Nanjing University of Science and Technology
2016
California Institute of Technology
2011
University of Colorado Denver
2008-2010
University of Michigan
2006-2010
Colorado State University
2008-2010
University of Colorado Cancer Center
2008-2010
A successful structure-based design of a class non-peptide small-molecule MDM2 inhibitors targeting the p53-MDM2 protein-protein interaction is reported. The most potent compound 1d binds to protein with Ki value 86 nM and 18 times more than natural p53 peptide (residues 16-27). Compound in inhibition cell growth LNCaP prostate cancer cells wild-type shows only weak activity PC-3 deleted p53. Importantly, has minimal toxicity normal epithelial cells. Our studies provide convincing example...
To better understand the role of irisin in humans, we examined effects human primary adipocytes and fresh subcutaneous white adipose tissue (scWAT). Human derived from 28 female donors' scWAT were used to examine on browning mitochondrial respiration, preadipocytes adipogenesis osteogenesis. Cultured fragments perirenal brown fat for investigating signal transduction pathways that mediate irisin's effect by Western blotting detect phosphorylated forms p38, ERK, STAT3 as well uncoupling...
The lichen cyanobacterial symbiont Nostoc sp. ATCC 53789 and its close relative GSV 224 are prolific producers of natural products, generating >25 derivatives the cryptophycin class secondary metabolites. Cryptophycin 1, prototypic member class, is a potent tubulin-depolymerizing agent, several semisynthetic being developed as anticancer therapeutics. Here we provide detailed characterization metabolic pathway by stable-isotope labeling experiments through cloning, sequencing, annotating...
Abstract Considered one of the most devastating coral disease outbreaks in history, stony tissue loss (SCTLD) is currently spreading throughout Florida’s reefs and greater Caribbean. SCTLD affects at least two dozen different species has been implicated extensive losses cover. Here we show Pseudoalteromonas sp. strain McH1-7 broad-spectrum antibacterial activity against SCTLD-associated bacterial isolates. Chemical analyses indicated produces potential antibacterials, korormicin...
Gene clusters, groups of physically adjacent genes that work collectively, are pivotal to bacterial fitness and valuable in biotechnology medicine. While various genome mining tools can identify characterize gene they often overlook their evolutionary diversity, a crucial factor revealing novel cluster functions applications. To address this gap, we developed GATOR-GC, targeted tool enables comprehensive flexible exploration clusters single execution. We show GATOR-GC identified diversity...
Stephacidin and notoamide natural products belong to a group of prenylated indole alkaloids containing core bicyclo[2.2.2]diazaoctane ring system. These bioactive fungal secondary metabolites have range unusual structural stereochemical features but their biosynthesis has remained uncharacterized. Herein, we report the first biosynthetic gene cluster for this class based on whole genome sequencing marine-derived Aspergillus sp. Two central pathway enzymes catalyzing both normal reverse...
Exercise offers short-term and long-term health benefits, including an increased metabolic rate energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates conversion of white into brown adipocytes as well mitochondrial biogenesis expenditure. Remarkably, irisin is highly expressed myocardium, but its physiological effects the heart are unknown. objective this work to investigate irisin's potential multifaceted on cardiomyoblasts For purpose, H9C2...
Mycosporine-like amino acids (MAAs) are secondary metabolites of a variety marine organisms including cyanobacteria and macroalgae. These compounds have strong ultraviolet (UV) absorption maxima between 310 362 nm biological sunscreens for counteracting the damaging effects UV radiation in nature. The common MAA shinorine has been used as one key active ingredient environmentally friendly sunscreen creams. Commercially is isolated from red algae that generally harvested wild. Here, we...
Over the last 25 years, biology has entered genomic era and is becoming a science of 'big data'. Most interpretations analyses rely on accurate functional annotations proteins encoded by more than 500 000 genomes sequenced to date. By different estimates, only half predicted carry an annotation, this percentage varies drastically between organismal lineages. Such large gap in knowledge hampers all aspects biological enterprise and, thereby, standing way reaching its full potential. A...
Dolastatin 10, a potent tubulin-targeting marine anticancer natural product, provided the basis for development of six FDA-approved antibody–drug conjugates. Through screening cyanobacterial Caldora penicillata environmental DNA libraries and metagenome sequencing, we identified its biosynthetic gene cluster. Functional prediction 10 enzymes encoded in 39 kb cluster supports dolastatin biosynthesis. The nonheme diiron monooxygenase DolJ was biochemically characterized to mediate terminal...
Genome sequencing revealed that Streptomyces sp. can dedicate up to ~ 10% of their genomes for the biosynthesis bioactive secondary metabolites. However, majority these biosynthetic gene clusters are only weakly expressed or not at all. Indeed, natural products is highly regulated through integrating multiple nutritional and environmental signals perceived by pleiotropic pathway-specific transcriptional regulators. Although refactoring has been a proved, productive approach activation...
The biomimetic total syntheses of both malbrancheamide and B are reported. synthesis the two monochloro species enabled structure to be unambiguously assigned. each feature an intramolecular Diels-Alder reaction a 5-hydroxypyrazin-2(1H)-one construct bicyclo[2.2.2]diazaoctane core, which has also been proposed as biosynthetic route these compounds.
Nitroaromatics are among the most important and commonly used chemicals but their production often suffers from multiple unsolved challenges. We have previously described development of biocatalytic nitration processes driven by an engineered P450 TxtE fusion construct. Herein we report creation improved biocatalysts through constructing characterizing proteins with reductase domain CYP102A1 (P450BM3, BM3R). The majority constructs contained variable linker length while one was rationally...
Approximately 10 Streptomyces species cause disease on underground plant structures. The most economically important of these is potato scab, and the studied pathogens scabiei (syn. S. scabies). main pathogenicity determinant scab-causing a nitrated diketopiperazine, known as thaxtomin A (ThxA). In pathogenic turgidiscabies, ThxA biosynthetic genes reside mobile island (PAI). However, mobilization PAIs in other remains uncharacterized. Here, we investigated PAI 87-22. Based whole genome...
Waikikiamides A-C (
Two natural auxins, phenylacetic acid (PAA) and indole-3-acetic (IAA), play crucial roles in plant growth development. One route of IAA biosynthesis uses the glucosinolate intermediate indole-3-acetaldoxime (IAOx) as a precursor, which is thought to occur only glucosinolate-producing plants Brassicales. A recent study showed that overproducing phenylacetaldoxime (PAOx) Arabidopsis increases PAA production. However, it remains unknown whether this increased resulted from hydrolysis...
Mycosporine-like amino acids (MAAs) are a family of natural products that produced by variety organisms for protection from ultraviolet damage. In this work, we combined different bioinformatic approaches to assess the distribution MAA biosynthesis and identified putative gene cluster Nostoc linckia NIES-25 encodes short-chain dehydrogenase/reductase nonheme iron(II)- 2-oxoglutarate-dependent oxygenase (MysH) as potential new biosynthetic enzymes. Heterologous expression refactored clusters...
Abstract Morphological profiling is a valuable tool in phenotypic drug discovery. The advent of high-throughput automated imaging has enabled the capturing wide range morphological features cells or organisms response to perturbations at single-cell resolution. Concurrently, significant advances machine learning and deep learning, especially computer vision, have led substantial improvements analyzing large-scale high-content images high throughput. These efforts facilitated understanding...
Cryptophycins (Crp) are a group of cyanobacterial depsipeptides with activity against drug-resistant tumors. Although they have been shown to be promising, further efforts required return these highly potent compounds the clinic through new generation analogues improved medicinal properties. Herein, we report chemosynthetic route relying on multifunctional enzyme CrpD-M2 that incorporates 2-hydroxy acid moiety (unit D) into Crp analogues. is unique non-ribosomal peptide synthetase (NRPS)...
Abstract Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important family of natural products. Their biosynthesis follows a common scheme in which the leader peptide precursor guides modifications single core peptide. Here we describe biochemical studies processing multiple within peptide, rare RiPP biosynthesis. In cyanobacterial microviridin pathway, ATP-grasp ligase, AMdnC, installs up to two macrolactones on each three AMdnA. The enzyme catalysis occurs...