A5048518576- CRISPR and Genetic Engineering
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Antibiotic Resistance in Bacteria
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Microbial Metabolism and Applications
- Plant biochemistry and biosynthesis
- Advanced biosensing and bioanalysis techniques
- Drug Transport and Resistance Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Plant-Microbe Interactions and Immunity
- Insect symbiosis and bacterial influences
- Fungal Biology and Applications
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Fungal and yeast genetics research
- Synthesis and Biological Evaluation
- SARS-CoV-2 and COVID-19 Research
- Plant Pathogens and Fungal Diseases
- Berberine and alkaloids research
- bioluminescence and chemiluminescence research
Shanghai Jiao Tong University
2020-2024
Novo Nordisk Foundation
2014-2021
Technical University of Denmark
2014-2021
Institute of Microbiology
2010-2021
Chinese Academy of Sciences
2010-2021
East China University of Science and Technology
2020
Novo Nordisk (Denmark)
2020
University of Chinese Academy of Sciences
2012-2016
Foundation Center
2015
Institute of Microbiology
2015
Bacteria of the order Actinomycetales are one most important sources pharmacologically active and industrially relevant secondary metabolites. Unfortunately, many them still recalcitrant to genetic manipulation, which is a bottleneck for systematic metabolic engineering. To facilitate manipulation actinomycetes, we developed highly efficient CRISPR-Cas9 system delete gene(s) or gene cluster(s), implement precise replacements, reversibly control expression in actinomycetes. We demonstrate our...
Abstract Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it not the of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved sense and respond sensitively a variety molecules benefit bacterial survival. By combining single-stranded cleavage ability competitive binding activities aTFs double-stranded DNA, here we develop simple, supersensitive, fast high-throughput platform...
It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. Here we provide bioinformatic and experimental evidence supporting this hypothesis. We identify proteobacteria, including pathogens, appear to be closely related actinobacterial ARGs known confer against clinically important antibiotics. Furthermore, two potential examples of recent horizontal transfer proteobacterial pathogens. Based on...
Streptomycetes serve as major producers of various pharmacologically and industrially important natural products. Although CRISPR-Cas9 systems have been developed for more robust genetic manipulations, concerns genome instability caused by the DNA double-strand breaks (DSBs) toxicity Cas9 remain. To overcome these limitations, here we report development DSB-free, single-nucleotide–resolution editing system CRISPR-BEST (CRISPR-Base Editing SysTem), which comprises a cytidine (CRISPR-cBEST) an...
Abstract Specialized or secondary metabolites are small molecules of biological origin, often showing potent activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis these natural products is governed by sets co-regulated physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs a standardized machine-readable way, Minimum Information Biosynthetic Gene cluster (MIBiG) data standard repository was initiated...
Phenotypic transitions play critical roles in host adaptation, virulence, and sexual reproduction pathogenic fungi. A minority of natural isolates Candida albicans, which are homozygous at the mating type locus (MTL, a/a or α/α), known to be able switch between two distinct cell types: white opaque. It is puzzling that white-opaque switching has never been observed majority C. albicans strains have heterozygous MTL genotypes (a/α), given they contain all opaque-specific genes essential for...
Abstract CRISPR base editing is a powerful method to engineer bacterial genomes. However, it restricts single-nucleotide substitutions. Here, address this challenge, we adapt CRISPR-Prime Editing-based, DSB-free, versatile, and resolution genetic manipulation toolkit for prokaryotes. It can introduce substitutions, deletions, insertions, the combination thereof, both in plasmids chromosome of E. coli with high fidelity. Notably, under optimal conditions, efficiency 1-bp deletions reach up...
Abstract Direct cloning of biosynthetic gene clusters (BGCs) from microbial genomes facilitates natural product-based drug discovery. Here, by combining Cas12a and the advanced features bacterial artificial chromosome library construction, we developed a fast yet efficient in vitro platform for directly capturing large BGCs, named CAT-FISHING (CRISPR/Cas12a-mediated direct cluster cloning). As demonstrations, several BGCs different actinomycetal genomic DNA samples were efficiently captured...
Five new polyketide derivatives, 7-O-methylkoninginin D (1) and trichodermaketones A−D (2−5), together with four known compounds, koninginins A, D, E, F, were isolated from the marine-derived fungus Trichoderma koningii. Trichodermaketones A (2) B (3) are unprecedented polyketides a bistetrafuran-containing tricyclic skeleton. The chemical structures absolute configurations of compounds 1−5 elucidated by comparing literature data extensive spectroscopic methods, including 2D NMR CD analysis....
Candida albicans is the most common human fungal pathogen, causing not only superficial infections, but also life-threatening systemic disease. C. can grow in several morphological forms including unicellular yeast-form, elongated hyphae and pseudohyphae. In certain natural environments, exists as biofilms, which are structured surface-attached microbial communities. Transcription factors play a critical role morphogenesis biofilm development. this study, we identified four...
ABSTRACT Pathogenic fungi are capable of switching between different phenotypes, each which has a biological advantage. In the most prevalent human fungal pathogen, Candida albicans , phenotypic transitions not only improve its adaptation to continuously changing host microenvironment but also regulate sexual mating. this report, we show that tropicalis another important opportunistic undergoes reversible and heritable switching, referred as “white-opaque” transition. Here N...
CRISPR tools, especially Cas9n-sgRNA guided cytidine deaminase base editors such as CRISPR-BEST, have dramatically simplified genetic manipulation of streptomycetes. One major advantage editing technology is the possibility to multiplex experiments in genomically instable species. Here, we demonstrate scaled up Csy4 based multiplexed genome using CRISPR-mcBEST Streptomyces coelicolor. We evaluated system by simultaneously targeting 9, 18, and finally all 28 predicted specialized metabolite...
Three new alkaloids, including auranomides A and B (1 2), a scaffold containing quinazolin-4-one substituted with pyrrolidin-2-iminium moiety, auranomide C (3), as well two known metabolites auranthine (4) aurantiomides (5) were isolated from the marine-derived fungus Penicillium aurantiogriseum. The chemical structures of compounds 1–3 elucidated by extensive spectroscopic methods, IR, HRESIMS 2D NMR analysis. absolute configurations suggested perspective plausible biosynthesis pathway....
Clinical use of antimicrobials faces great challenges from the emergence multidrug-resistant pathogens. The overexpression drug efflux pumps is one major contributors to multidrug resistance (MDR). Reversing function a promising approach overcome MDR. In life-threatening fungal pathogen Candida albicans, facilitator superfamily (MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading Here we report counterintuitive case reversing MDR in C. albicans by using...
The human fungal pathogen Candida albicans has at least two types of morphological transitions: white to opaque cell transitions and yeast hyphal transitions. Opaque cells have historically not been known undergo filamentation under standard filament-inducing conditions. Here we find that Bcr1 its downstream regulators Cup9, Nrg1 Czf1 the cAMP-signalling pathway control in C. albicans. We shown deletion BCR1, CUP9, NRG1 CZF1 results culture Disruption BCR1 no obvious effect on growth,...