- Microbial Natural Products and Biosynthesis
- Fungal Biology and Applications
- Plant biochemistry and biosynthesis
- Steroid Chemistry and Biochemistry
- Microbial Metabolic Engineering and Bioproduction
- Natural product bioactivities and synthesis
- Pharmacological Effects of Natural Compounds
- Plant Pathogens and Fungal Diseases
- Chemical synthesis and alkaloids
- Microbial Metabolism and Applications
- Carbohydrate Chemistry and Synthesis
- Food Allergy and Anaphylaxis Research
- Probiotics and Fermented Foods
- Phytochemistry and Biological Activities
- Microbial Metabolites in Food Biotechnology
- Phytochemical Studies and Bioactivities
- Transgenic Plants and Applications
- Bioactive Compounds and Antitumor Agents
- Synthetic Organic Chemistry Methods
- Polyamine Metabolism and Applications
- Plant Gene Expression Analysis
- Phytochemical compounds biological activities
- Enzyme Production and Characterization
- Alkaloids: synthesis and pharmacology
- Phytochemistry and Bioactive Compounds
Utah State University
2015-2024
Hunan University of Traditional Chinese Medicine
2016-2019
Hunan University
2018
East China University of Science and Technology
2002-2017
Peking University
2002-2017
In-Q-Tel
2012
University of California, Los Angeles
2007-2009
Icahn School of Medicine at Mount Sinai
2009
University of Arizona
2004-2008
University of Southern California
2007-2008
Wound-healing assay-guided fractionation of an EtOAc extract the fungal strain Fusarium oxysporum EPH2RAA endophytic in Ephedra fasciculata afforded beauvericin (1), (−)-oxysporidinone (2), and two new N-methyl-2-pyridones, (−)-4,6'-anhydrooxysporidinone (3) (−)-6-deoxyoxysporidinone (4). Beauvericin (1) inhibited migration metastatic prostate cancer (PC-3M) breast (MDA-MB-231) cells showed antiangiogenic activity HUVEC-2 at sublethal concentrations. Cytotoxicity-guided F. CECIS occurring...
ABSTRACT The beneficial bacterium Pseudomonas chlororaphis O6 produces indole-3-acetic acid (IAA), a plant growth regulator. However, the pathway involved in IAA production this has not been reported. In paper we describe involvement of indole-3-acetamide (IAM) P. and effects CuO ZnO nanoparticles (NPs). Sublethal levels NPs differentially affected secreted medium containing tryptophan as precursor. After 15 h growth, NP-exposed cells had metabolized more than control NP-challenged cells....
Significance Benzenediol lactone (BDL) polyketides are privileged structures whose various members bind to distinct receptors or modulate the heat shock response and immune system. BDLs biosynthesized by collaborating polyketide synthase enzyme pairs in fungi. Coexpressing random heterocombinations of these enzymes from different BDL biosynthetic pathways yeast cells is shown here lead one-pot, one-step combinatorial biosynthesis structurally diverse practical amounts. Combinatorial promises...
In a study to discover potential anticancer agents from rhizosphere fungi of Sonoran desert plants cytotoxic EtOAc extracts four Aspergillus strains have been investigated. Two new metabolites, terrequinone A (1) and terrefuranone (2), along with Na-acetyl aszonalemin (LL-S490β) (3) were isolated As. terreus occurring in the Ambrosia ambrosoides, whereas inhabiting an unidentified Brickellia sp. afforded dehydrocurvularin (4), 11-methoxycurvularin (5), 11-hydroxycurvularin (6). cervinus...
Resorcylic acid lactones represent a unique class of fungal polyketides and display wide range biological activities, such as nanomolar inhibitors Hsp90 MAP kinase. The biosynthesis these compounds is proposed to involve two polyketide synthases (PKS) that function collaboratively yield 14-membered macrolactone with resorcylate core. We report here the reconstitution Gibberella zeae PKS13, which nonreducing PKS associated zearalenone biosynthesis. Using small molecule mimic natural...
A novel halogenating agent: fungal halogenase Rdc2 from Pochonia chlamydosporia has been reconstituted in E. coli and biochemically characterized as the dedicated radicicol biosynthesis. The enzyme displays broad substrate specificity towards molecules such dihydroresorcylide (1) to generate mono- dihalogenated (X=Br or Cl) derivatives, thus representing a promising biocatalyst for natural product
Resorcylic acid lactones and dihydroxyphenylacetic represent important pharmacophores with heat shock response immune system modulatory activities. The biosynthesis of these fungal polyketides involves a pair collaborating iterative polyketide synthases (iPKSs): highly reducing iPKS product that is further elaborated by nonreducing (nrPKS) to yield 1,3-benzenediol moiety bridged macrolactone. Biosynthesis unreduced requires the sequestration programmed cyclization reactive poly-β-ketoacyl...
The phytotoxic fungal polyketides lasiodiplodin and resorcylide inhibit human blood coagulation factor XIIIa, mineralocorticoid receptors, prostaglandin biosynthesis. These secondary metabolites belong to the 12-membered resorcylic acid lactone (RAL12) subclass of benzenediol (BDL) family. Identification genomic loci for biosynthesis from Lasiodiplodia theobromae Acremonium zeae revealed collaborating iterative polyketide synthase (iPKS) pairs whose efficient heterologous expression in...
A crucial step during the programmed biosynthesis of fungal polyketide natural products is release final intermediate from iterative synthases (iPKSs), most frequently by a thioesterase (TE) domain. Realization combinatorial with iPKSs requires TE domains that can accept altered intermediates generated hybrid synthase enzymes and successfully "unnatural products" desired structure. Achieving precise control over product paramount importance O-C bond-forming capable macrocyclization,...
Endophytic microorganisms are a rich source of bioactive natural products. They considered as promising biofertilizers and biocontrol agents due to their growth-promoting interactions with the host plants secondary metabolites that can help manage plant pathogens. Identification new endophytes may lead discovery novel molecules or provide strains for production valuable compounds.In this study, we isolated an endophytic bacterium from leaves Taxus chinensis, which was identified Pseudomonas...
Precursor-directed biosynthesis was used to produce analogues of the cyclic depsipeptide mycotoxin beauvericin (1) using filamentous fungus Beauveria bassiana ATCC 7159. Feeding 30 d-2-hydroxyisovalerate and l-phenylalanine, natural 2-hydroxycarboxylic acid amino precursors beauvericin, led novel beauvericins. Six these were isolated characterized, their cytotoxicity directional cell migration (haptotaxis) inhibitory activity against metastatic prostate cancer line PC-3M evaluated....
Iterative fungal polyketide synthases (PKSs) use a unique set of biochemical rules in the synthesis complex polyketides. These dictate starter unit selection, chain length control, and post-PKS processing. We have demonstrated E. coli expression reconstitution an iterative, unreduced PKS. The Gibberella fujikuroi PKS4 was expressed at high levels, purified to homogeneity, functionally characterized. In presence malonyl-CoA, able synthesize nonaketide...
Abstract Nonribosomal peptide synthetases (NRPSs) assemble a large group of structurally and functionally diverse natural products. While the iterative catalytic mechanism bacterial NRPSs is known, it remains unclear how fungal create products desired length. Here we show that adopt an alternate incorporation strategy. Beauvericin bassianolide have same C 1 -A -T -C 2 -MT-T 2a 2b 3 domain organization. During catalysis, take turns to incorporate two biosynthetic precursors into growing...
The cyclohexenone ring A of tetracyclines exhibits unique structural features not observed among other aromatic polyketides. These substitutions include the C2 primary amide, C4 dimethylamine, and C12a tertiary alcohol. Here we report identification reconstitution minimum set enzymes required for biosynthesis anhydrotetracycline (ATC, 5), first intermediate in tetracycline biosynthetic pathway that contains fully functionalized A. Using a combination vivo vitro approaches, confirmed OxyL,...
Regiospecific cyclizations of the nascent poly-beta-ketone backbones dictate structures polyketide natural products. The fungal iterative megasynthases use terminal thioesterase/claisen cyclase (TE/CLC) domains to direct fate chains. In this work, we present two strategies toward redirecting cyclization steps PKSs using Gibberella fujikuroi PKS4. First, inactivation or removal TE/CLC domain resulted in synthesis new SMA93 2. Complementation mutant PKS4 with a standalone restored...