A5051781729- Microbial Natural Products and Biosynthesis
- Fungal Biology and Applications
- Fungal and yeast genetics research
- Plant biochemistry and biosynthesis
- Microbial Metabolism and Applications
- Plant Pathogens and Fungal Diseases
- Spaceflight effects on biology
- Polar Research and Ecology
- Microbial Community Ecology and Physiology
- Marine Sponges and Natural Products
- Protist diversity and phylogeny
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Mycotoxins in Agriculture and Food
- Cancer-related Molecular Pathways
- Antifungal resistance and susceptibility
- 14-3-3 protein interactions
- Chemical Synthesis and Analysis
- Bioeconomy and Sustainability Development
- Plant-Microbe Interactions and Immunity
- Space Exploration and Technology
- Algal biology and biofuel production
- Synthetic Organic Chemistry Methods
- Cancer Treatment and Pharmacology
- DNA and Nucleic Acid Chemistry
University of Southern California
2016-2025
Southern California University for Professional Studies
2013-2025
Los Angeles City College
2015-2019
Soochow University
2013-2015
University of Kansas
2012-2015
Chia Nan University of Pharmacy and Science
2008-2013
Pacific Northwest National Laboratory
2012-2013
Hokkaido University
2009
Allergan (United States)
2009
The Ohio State University
2009
The genome sequencing of Aspergillus species including A. nidulans reveals that the products many secondary metabolism pathways in these fungi have not been elucidated. Our examination 27 polyketide synthases (PKS) revealed one highly reduced PKS (HR-PKS, AN1034.3) and nonreduced (NR-PKS, AN1036.3) are located next to each other genome. Since no known metabolites could be produced by two enzymes, we hypothesized this cryptic gene cluster produces an unknown natural product. Indeed after...
Meroterpenoids are a class of fungal natural products that produced from polyketide and terpenoid precursors. An understanding meroterpenoid biosynthesis at the genetic level should facilitate engineering second-generation molecules increasing production first-generation compounds. The filamentous fungus Aspergillus nidulans has previously been found to produce two meroterpenoids, austinol dehydroaustinol. Using targeted deletions we created, have determined that, surprisingly, separate gene...
Fungal secondary metabolites (SMs) are an important source of medically valuable compounds. Genome projects have revealed that fungi many SM biosynthetic gene clusters not normally expressed. To access these potentially valuable, cryptic clusters, we developed a heterologous expression system in Aspergillus nidulans . We efficient for amplifying genes from target fungus, placing them under control regulatable promoter, transferring into A. , and expressing them. validated this by nonreducing...
Significance Filamentous fungi are well known for their ability to produce a wide range of natural products. Until now, biosynthetic genes contiguously aligned in cluster have been associated with the production distinct product. This work demonstrates an additional layer complexity fungal secondary-metabolite gene clusters. In contrast view stand-alone clusters, our collective data revealed existence superclusters intertwined involved formation more than one chemical Comparative genomics...
Deletion of cclA, a component the COMPASS complex Aspergillus nidulans, results in production monodictyphenone and emodin derivatives. Through set targeted deletions cclA deletion strain, we have identified genes required for analog biosynthesis. Identification an intermediate, endocrocin, from mdpHDelta strain suggests that mdpH might encode decarboxylase. Furthermore, by replacing promoter mdpA (a putative aflJ homolog) mdpE aflR with inducible alcA promoter, confirmed MdpA functions as...
Abstract To reduce the secondary metabolite background in Aspergillus nidulans and minimize rediscovery of compounds pathway intermediates, we created a “genetic dereplication” strain which deleted eight most highly expressed gene clusters (more than 244,000 base pairs total). This allowed us to discover novel compound that designate aspercryptin propose biosynthetic for compound. Interestingly, is formed from produced by two separate clusters, one makes well‐known product cichorine. raises...
Xanthones are a class of molecules that bind to number drug targets and possess myriad biological properties. An understanding xanthone biosynthesis at the genetic level should facilitate engineering second-generation increasing production first-generation compounds. The filamentous fungus Aspergillus nidulans has been found produce two prenylated xanthones, shamixanthone emericellin, we report discovery more, variecoxanthone A epishamixanthone. Using targeted deletions created, determined...
Genome sequencing has revealed that fungi have the ability to synthesize many more natural products (NPs) than are currently known, but methods for obtaining suitable expression of NPs been inadequate. We developed a successful strategy bypasses normal regulatory mechanisms. By efficient gene targeting, we replaced, en masse, promoters nonreducing polyketide synthase (NR-PKS) genes, key genes in NP biosynthetic pathways, and other necessary NR-PKS product formation or release. This allowed...
The sequencing of Aspergillus genomes has revealed that the products a large number secondary metabolism pathways have not yet been identified. This is probably because many metabolite gene clusters are expressed under normal laboratory culture conditions. It is, therefore, important to discover conditions or regulatory factors can induce expression these genes. We report deletion sumO, encodes small ubiquitin-like protein SUMO in A. nidulans, caused dramatic increase production asperthecin...
F-9775A and F-9775B are cathepsin K inhibitors that arise from a chromatin remodelling deletant strain of Aspergillus nidulans. A polyketide synthase gene has been determined to be responsible for their formation the simpler, archetypical orsellinic acid. We have discovered simple culture conditions result in production three compounds, this facilitates analysis genes synthesis. now analysed F9775/orsellinic acid cluster using set targeted deletions. find alone is required biosynthesis only...
Hepatic stellate cells (HSCs) undergo myofibroblastic transdifferentiation (activation) to participate in liver fibrosis and identification of molecular targets for this cell fate regulation is essential development efficacious therapeutic modalities the disease. Peroxisomal proliferator-activated receptor γ (PPARγ) required differentiation HSCs its epigenetic repression underlies HSC activation. The herbal prescription Yang-Gan-Wan (YGW) prevents fibrosis, but active ingredients mechanisms...
Abstract The 6,6‐quinolone scaffold of the viridicatin‐type fungal alkaloids are found in various quinolone which often exhibit useful biological activities. Thus, it is interest to identify viridicatin‐forming enzymes and understand how such biosynthesized. Here an Aspergillal gene cluster responsible for biosynthesis 4′‐methoxyviridicatin was identified. Detailed vitro studies led discovery dioxygenase AsqJ performs two distinct oxidations: first desaturation form a double bond then...
Fungal genome projects are revealing thousands of cryptic secondary metabolism (SM) biosynthetic gene clusters that encode pathways potentially produce valuable compounds. Heterologous expression systems should allow these to be expressed and their products obtained, but approaches needed identify the most target clusters. The inp cluster Aspergillus nidulans contains a gene, inpE, encodes proteasome subunit, leading us hypothesize produces inhibitor inpE confers resistance this compound....
Abstract The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses changing microenvironments. Traditional metabolomics methods are ill-equipped probe a wide variety of environments or environmental dynamics. Here we introduce class microscale culture platforms analyse diversity fungal and bacterial metabolomes. By leveraging stable biphasic interfaces integrate microculture with small molecule isolation via liquid–liquid...
As durations of manned space missions increase, it is imperative to understand the long-term consequence microbial exposure on human health in a closed habitat. To date, studies aimed at bacterial and fungal contamination vessels have highlighted species compositions biased toward hardy, persistent organisms capable withstanding harsh conditions. In current study, we assessed traits two independent Aspergillus fumigatus strains isolated from International Space Station. Ubiquitously found...