Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905.

The genome sequencing of Aspergillus terreus reveals that the vast number of predicted biosynthetic gene clusters have not reflected by the metabolic profile observed under conventional culture conditions. In this study, a silent azaphilone biosynthetic gene cluster was activated by overexpressing a pathway-specific transcription factor gene2642 in marine-derived fungus A. terreus RA2905.

Structural Optimization of Marine Natural Product Pretrichodermamide B for the Treatment of Colon Cancer by Targeting the JAK/STAT3 Signaling Pathway.

Marine natural product (MNP) pretrichodermamide B (Pre B, ) was identified as a novel STAT3 inhibitor in our previous work, while its metabolic instability hindered its further development. To address this drawback, ligand structure-based drug design was adopted leading to a series of Pre B derivatives. Among them, MNP trichodermamide B (tri B, ) obtained by skeletal rearrangement exhibited more potent antiproliferative activity with an IC value of 0.

Screening and genetic engineering of marine-derived Aspergillus terreus for high-efficient production of lovastatin.

Background: Lovastatin has widespread applications thanks to its multiple pharmacological effects. Fermentation by filamentous fungi represents the major way of lovastatin production. However, the current lovastatin productivity by fungal fermentation is limited and needs to be improved.

The Histone Deacetylase HstD Regulates Fungal Growth, Development and Secondary Metabolite Biosynthesis in .

Histone acetylation modification significantly affects secondary metabolism in filamentous fungi. However, how histone acetylation regulates secondary metabolite synthesis in the lovastatin (a lipid-lowering drug) producing remains unknown because protein is involved and has been identified in this species. Here, the fungal-specific histone deacetylase gene, , was characterized through functional genomics in two marine-derived strains, Mj106 and RA2905.

Development of a rapid detection method for by using CRISPR-Cas12a.

Harmful algal blooms (HABs), mainly formed by dinoflagellates, have detrimental effects on marine ecosystems and public health. Therefore, detecting HABs is crucial for early warning and prevention of HABs as well as the mitigation of their adverse effects. Although various methods, such as light microscopy, electron microscopy, real-time PCR, and microarrays, have already been established for the detection of HABs, they are still cumbersome to be exploited in the field.

Sclerotioloids A-C: Three New Alkaloids from the Marine-Derived Fungus ST0501.

Alkaloids, as one of the largest classes of natural products with diverse structures, are an important source of innovative medicines. Filamentous fungi, especially those derived from the marine environment, are one of the major producers of alkaloids. In this study, three new alkaloids, sclerotioloids A-C (-), along with six known analogs (-), were obtained under the guidance of the MS/MS-based molecular networking from the marine-derived fungus, ST0501, collected from the South China Sea.

Bioactive Alpha-Pyrone and Phenolic Glucosides from the Marine-Derived sp. P2100.

Glycoside compounds have attracted great interest due to their remarkable and multifarious bioactivities. In this study, four hitherto unknown 4-methoxy--D-glucosyl derivatives were obtained and identified from the marine-derived fungus sp. P2100, including three alpha-pyrone glycosides (-) and one phenolic glycoside ().

Bioactive Alkaloids from the Marine-Derived Fungus sp. P2100.

The fungal species are considered the prolific producers of bioactive secondary metabolites with a variety of chemical structures. In this study, the biosynthetic potential of marine-derived fungus sp. P2100 to produce bioactive alkaloids was explored by using the one strain many compounds (OSMAC) strategy.

Induction of Secondary Metabolite Biosynthesis by Deleting the Histone Deacetylase HdaA in the Marine-Derived Fungus RA2905.

is well-known for its ability to biosynthesize valuable pharmaceuticals as well as structurally unique secondary metabolites. However, numerous promising cryptic secondary metabolites in this strain regulated by silent gene clusters remain unidentified. In this study, to further explore the secondary metabolite potential of , the essential histone deacetylase gene was deleted in the marine-derived RA2905.

Enhanced production of terrein in marine-derived Aspergillus terreus by refactoring both global and pathway-specific transcription factors.

Background: Terrein, a major secondary metabolite from Aspergillus terreus, shows great potentials in biomedical and agricultural applications. However, the low fermentation yield of terrein in wild A. terreus strains limits its industrial applications.

Development of versatile and efficient genetic tools for the marine-derived fungus Aspergillus terreus RA2905.

Marine-derived Aspergillus terreus produces a variety of structurally novel secondary metabolites, most of which show unique biological activities. However, the lack of efficient genetic tools limits the discovery of new compounds, the elucidation of involved biosynthesis mechanism, as well as the strain engineering efforts. Therefore, in this study, we first established both an effective PEG-mediated chemical transformation system of protoplasts and an electroporation system of conidia in a marine-derived fungus A.

Subchronic toxicity of dietary sulfamethazine and nanoplastics in marine medaka (Oryzias melastigma): Insights from the gut microbiota and intestinal oxidative status.

Antibiotics and nanoplastics are two prevalent pollutants in oceans, posing a great threat to marine ecosystems. As antibiotics and nanoplastics are highly bioconcentrated in lower trophic levels, evaluating their impacts on marine organisms via dietary exposure route is of great importance. In this study, the individual and joint effects of dietborne sulfamethazine (SMZ) and nanoplastic fragments (polystyrene, PS) in marine medaka (Oryzias melastigma) were investigated.

Genomic and Chemical Investigation of Bioactive Secondary Metabolites From a Marine-Derived Fungus P2648.

Marine fungi of the genus are rich resources of secondary metabolites, showing a variety of biological activities. Our anti-bacterial screening revealed that the crude extract from a coral-derived fungus P2648 showed strong activity against some pathogenic bacteria. Genome sequencing and mining uncovered that there are 28 secondary metabolite gene clusters in P2648, potentially involved in the biosynthesis of antibacterial compounds.

Benzyl Furanones and Pyrones from the Marine-Derived Fungus Induced by Chemical Epigenetic Modification.

Chemical epigenetic modification on a marine-derived fungus RA2905 using a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), resulted in a significantly changed metabolic profile. A chemical investigation of its ethyl acetate (EtOAc) extract led to the isolation of a racemate of benzyl furanone racemate (±)-, which further separated chirally as a pair of new enantiomers, (+)- and (-)-asperfuranone (), together with two new benzyl pyrones, asperpyranones A () and B (). Their structures were elucidated by analysis of the comprehensive spectroscopic data, including one-dimensional (1D) and two-dimensional (2D) NMR, and HRESIMS.

New Thiodiketopiperazine and 3,4-Dihydroisocoumarin Derivatives from the Marine-Derived Fungus .

has been reported to produce many secondary metabolites that exhibit potential bioactivities, such as antibiotic, hypoglycemic, and lipid-lowering activities. In the present study, two new thiodiketopiperazines, emestrins L () and M (), together with five known analogues (-), and five known dihydroisocoumarins (-), were obtained from the marine-derived fungus RA2905. The structures of the new compounds were elucidated by analysis of the comprehensive spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) data.

Epigenetic Agents Trigger the Production of Bioactive Nucleoside Derivatives and Bisabolane Sesquiterpenes From the Marine-Derived Fungus .

Epigenetic agents, histone deacetylase inhibitor (SAHA) and DNA methyltransferase inhibitor (5-Aza), were added to Czapek-Dox medium to trigger the chemical diversity of marinederived fungus XS-20090066. By HPLC and H NMR analysis, the diversity of fungal secondary metabolites was significantly increased compared with the control. With the aid of MS/MS-based molecular networking, two new nucleoside derivatives, kipukasins K () and L () were obtained.

Exploration of the Regulatory Mechanism of Secondary Metabolism by Comparative Transcriptomics in .

Mycotoxins cause a huge threaten to agriculture, food safety, and human and animal life. Among them, aflatoxins (AFs) have always been considered the most potent carcinogens, and filamentous fungi from genus are their major producers, especially . Although the biosynthesis path of these chemicals had been well-identified, the regulatory mechanisms controlling expression of AF gene cluster were poorly understood.

Contribution of peroxisomal protein importer AflPex5 to development and pathogenesis in the fungus Aspergillus flavus.

Peroxisomes are important organelles that have diverse metabolic functions and participate in the pathogenicity of fungal pathogens. Previous studies indicate that most functions of peroxisomes are dependent on peroxisomal matrix proteins, which are delivered from the cytoplasm into peroxisomes by peroxisomal protein importers. In this study, the roles of peroxisomal protein importer AflPex5 were investigated in Aspergillus flavus with the application of gene disruption.

Essential APSES Transcription Factors for Mycotoxin Synthesis, Fungal Development, and Pathogenicity in .

Aflatoxins are a potent carcinogenic mycotoxin and has become a research model of fungal secondary metabolism (SM). Via systematically investigating the APSES transcription factors (TFs), two APSES proteins were identified: AfRafA and AfStuA. These play central roles in the synthesis of mycotoxins including aflatoxin and cyclopiazonic acid, and fungal development and are consequently central to the pathogenicity of the aflatoxigenic .

Putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression.

The morphological development of fungi is a complex process and is often coupled with secondary metabolite production. In this study, we assessed the function of putative methyltransferase LaeA and transcription factor CreA in controlling asexual development and secondary metabolic gene cluster expression in Penicillium oxalicum. The deletion of laeA (ΔlaeA) impaired the conidiation in P.

Production of a high-efficiency cellulase complex via β-glucosidase engineering in Penicillium oxalicum.

Background: Trichoderma reesei is a widely used model cellulolytic fungus, supplying a highly effective cellulase production system. Recently, the biofuel industry discovered filamentous fungi from the Penicillium genus as a promising alternative to T. reesei.

A novel bZIP transcription factor ClrC positively regulates multiple stress responses, conidiation and cellulase expression in Penicillium oxalicum.

Cellulase production in filamentous fungi is largely regulated at the transcriptional level, and several transcription factors have been reported to be involved in this process. In this study, we identified ClrC, a novel transcription factor in cellulase production in Penicillium oxalicum. ClrC and its orthologs have a highly conserved basic leucine zipper (bZIP) DNA binding domain, and their biological functions have not been explored.

Proteomic analysis of the biomass hydrolytic potentials of Penicillium oxalicum lignocellulolytic enzyme system.

Background: The mining of high-performance enzyme systems is necessary to develop industrial lignocellulose bioconversion. Large amounts of cellulases and hemicellulases can be produced by Penicillium oxalicum. Hence, the enzyme system of this hypercellulolytic fungus should be elucidated to help design optimum enzyme systems for effective biomass hydrolysis.

Penicillium oxalicum PoFlbC regulates fungal asexual development and is important for cellulase gene expression.

Filamentous fungi can initiate vegetative growth on complex plant polysaccharides in nature through secreting a large amount of lignocellulose-degrading enzymes. These fungi develop a large amount of asexual spores to disperse and survive under harsh conditions, such as carbon and nitrogen depletion. Numerous studies report the presence of a cross-talk between asexual development and extracellular enzyme production, especially at the regulation level.

Synergistic and Dose-Controlled Regulation of Cellulase Gene Expression in Penicillium oxalicum.

Filamentous fungus Penicillium oxalicum produces diverse lignocellulolytic enzymes, which are regulated by the combinations of many transcription factors. Here, a single-gene disruptant library for 470 transcription factors was constructed and systematically screened for cellulase production. Twenty transcription factors (including ClrB, CreA, XlnR, Ace1, AmyR, and 15 unknown proteins) were identified to play putative roles in the activation or repression of cellulase synthesis.