A5056986683- Microbial Natural Products and Biosynthesis
- Histone Deacetylase Inhibitors Research
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Fungal Biology and Applications
- Research on Leishmaniasis Studies
- Amino Acid Enzymes and Metabolism
- Enzyme Production and Characterization
- Enzyme Catalysis and Immobilization
- Trypanosoma species research and implications
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Genomics and Phylogenetic Studies
- Parasites and Host Interactions
- Marine Sponges and Natural Products
- Adenosine and Purinergic Signaling
- Glycosylation and Glycoproteins Research
- stochastic dynamics and bifurcation
- Copper-based nanomaterials and applications
- Polyamine Metabolism and Applications
- Biochemical and Structural Characterization
- Plant-Microbe Interactions and Immunity
- Robot Manipulation and Learning
- Quantum Dots Synthesis And Properties
- Autophagy in Disease and Therapy
University of California, Santa Barbara
2020-2025
Guangxi Academy of Agricultural Science
2024
Ministry of Agriculture and Rural Affairs
2024
University of California, Los Angeles
2017-2023
Children's Hospital of Chongqing Medical University
2023
Chongqing Medical University
2023
Inner Mongolia Medical University
2023
Xidian University
2023
Inner Mongolia Comprehensive Disease Prevention and Control Center
2023
Gansu Agricultural University
2023
Abstract Cationic polyamines such as spermidine and spermine are critical in all forms of life, they regulate the function biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation dysregulated associated with neoplastic diseases colon cancer, prostate cancer neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) a robust deacetylase, using recombinant enzymes from Homo sapiens (human) Danio rerio (zebrafish). The 2.85 Å-resolution...
A novel class of ZnSalens (ZnL(1-10)) with lipophilic and cationic conjugates as optical probes in single two-photon fluorescence microscopy images living cells were prepared, which exhibited chemo- photostability, low cytotoxicity high subcellular selectivity.
Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The of 1 is tetracyclic, cage-like, oxygenated sesquiterpene connected dimethylcadaverine via C–N bond acylated with 5,5-dimethyl-l-pipecolate. roles all are established...
Fusaric acid (FA) is a well-known mycotoxin that plays an important role in plant pathology. The biosynthetic gene cluster for FA has been identified, but the pathway remains unclarified. Here, we elucidated biosynthesis of FA, which features two-enzyme catalytic cascade, pyridoxal 5′-phosphate (PLP)-dependent enzyme (Fub7), and flavin mononucleotide (FMN)-dependent oxidase (Fub9) synthesizing picolinic scaffold. also involves off-line collaboration between highly reducing polyketide...
Abstract Pyridoxal 5’‐phosphate (PLP)‐dependent enzymes that catalyze γ‐replacement reactions are prevalent, yet their utilization of carbon nucleophile substrates is rare. The recent discovery two PLP‐dependent enzymes, CndF and Fub7, has unveiled unique C−C bond forming capabilities, enabling the biocatalytic synthesis alkyl‐ substituted pipecolic acids from O‐ acetyl‐L‐homoserine β‐keto acid or aldehyde derived enolates. This breakthrough presents fresh avenues for biosynthesis...
Rational design of effective photoactivatable/photoswitchable fluorophores, by introducing appropriate photoreactions to tune the electron transfer processes ground or/and excited states and switch fluorescence off/on, is crucial achieve high temporal spatial resolution in live cell (organism) imaging. Besides one photon activatable it highly desirable develop two fluorophores using light NIR or IR region, which reduces photodamage allows deep penetration into cells tissues. In this work, we...
1‐Aminocyclopropane‐1‐carboxylate synthase (ACCS) catalyzes the conversion of S ‐adenosyl‐methionine to 1‐aminocyclopropane‐1‐carboxylate (ACC), a rate‐limiting step in ethylene biosynthesis. A gene encoding putative ACCS protein was identified human genome two decades ago. It has been shown not exhibit any canonical ACC activity and its true function remains obscure. In this study, through biochemical profiling approach, we demonstrate that possesses cysteine conjugate sulfoxide β‐lyase...
Trichothecenes are a widespread family of sesquiterpenoid toxins that can pose significant risks to food and feed safety as well environmental health. A defining feature all trichothecenes is their central tricyclic 12,13-epoxytrichothec-9-ene (EPT) motif. Although the formation EPT skeleton has long been presumed be spontaneous process, nonenzymatic cyclization reaction forming tetrahydropyran ring in requires acid catalysis; otherwise, it occurs too slowly sustain efficient trichothecene...
Nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes have diverse functions in primary secondary metabolisms. By using a structure-guided approach, we uncovered the function of enzyme with unusual domain architecture, catalyzing two sequential two-electron reductions glycine betaine to choline. Structural analysis based on homology model suggests cation-π interactions as major substrate specificity determinant, which was verified analogs inhibitors. Bioinformatic indicates this...
Abstract Siderophores belonging to the ferrichrome family are essential for viability of fungal species and play a key role virulence numerous pathogenic fungi. Despite their biological significance, our understanding how these iron-chelating cyclic hexapeptides assembled by non-ribosomal peptide synthetase (NRPS) enzymes remains poorly understood, primarily due nonlinearity exhibited domain architecture. Herein, we report biochemical characterization SidC NRPS, responsible construction...
Previously, we have demonstrated that replacement of the strictly conserved glycine in collagen with aza-glycine provides a general solution for stabilizing triple helical peptides (Chenoweth, D. M.; et al. J. Am. Chem. Soc. 2016, 138, 9751 ; 2015, 137, 12422 ). The additional hydrogen bond and conformational constraints provided by increases thermal stability rate folding composed Pro-Hyp-Gly triplet repeats, allowing truncation to smallest self-assembling peptide systems observed date....
Autophagy is a complex, multi-step and biologically important pathway mediated by autophagosomes autolysosomes. Accurately dissecting detecting different stages of autophagy to elucidate its molecular mechanism thereby facilitate the discovery pharmaceutical molecules. We herein reported small-molecule synthetic probe, Zn-G4, which only fluorescent upon starvation- or chemical agent-induced within autolysosome possible late endosome/lysosome networks. The probe can be detected one-photon...
Truncated iterative polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) megasynthases in which only the C domain is present are widespread fungi, yet nearly all members have unknown functions. Bioinformatics analysis showed that domains of such PKS-C enzymes noncanonical due to substitution at second histidine active site HHxxxDG motif. Here, we used genome mining strategy characterize a cryptic hybrid from Talaromyces wortmanii and discovered products reduced long-chain...
Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate transform carboxylic acids in both primary secondary metabolism are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. Here, we show that catalyzes ATP-dependent unidirectional stereoinversion l-tryptophan d-tryptophan with complete conversion. While the catalyzed by epimerization (E) domain, terminal condensation (C) domain...
Siderophores play a vital role in the viability of fungi and are essential for virulence many pathogenic fungal species. Despite their importance physiology pathogenesis, programming rule siderophore assembly by nonribosomal peptide synthetases (NRPSs) remains unresolved. Here, we report characterization bimodular NRPS, SidD, responsible construction extracellular fusarinine C. The use intact protein mass spectrometry, together with vitro biochemical assays native dissected enzymes, provided...
A nonribosomal peptide synthetase (NRPS)-nonreducing polyketide synthase (NRPKS) hybrid enzyme (AnATPKS) from Aspergillus niger was shown to produce amino acid derived α-pyrone natural products (pyrophen and campyrone B). Biochemical characterization of the NRPS module in vitro reveals that adenylation domain is promiscuous toward a variety substituted phenylalanine analogues. Using precursor feeding heterologous expression AnATPKS an associated O-methyltransferase (AnOMT), we were able...
Hydroalkoxylation is a powerful and efficient method of forming C-O bonds cyclic ethers in synthetic chemistry. In studying the biosynthesis fungal natural product herqueinone, we identified an enzyme that can perform intramolecular enantioselective hydroalkoxylation reaction. PhnH catalyzes addition phenol to terminal olefin reverse prenyl group give dihydrobenzofuran product. The accelerates reaction by 3 × 105-fold compared uncatalyzed belongs superfamily proteins with domain unknown...