Selective inhibition of sterolO-acyltransferase 1 isozyme by beauveriolide III in intact cells

Ohshiro, Taichi; Kobayashi, Keisuke; Ohba, Mio; Matsuda, Daisuke; Rudel, Lawrence L.; Takahashi, Takashi; Doi, Takayuki; Tomoda, Hiroshi

doi:10.1038/s41598-017-04177-8

Cited by 21 publications

(20 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among them, beauveriolide I ( 21 ) displayed insecticidal activity on Spodoptera litura and Callosobruchus chinensis [ 36 ]. Beauveriolide III ( 23 ) selectively inhibited sterol O -acyltransferase 1 (SOAT1) in a cell-based assay [ 39 ].…”

Section: Cyclic Tetradepsipeptidesmentioning

confidence: 99%

Structural Diversity and Biological Activities of Cyclic Depsipeptides from Fungi

et al. 2018

View full text Add to dashboard Cite

Cyclic depsipeptides (CDPs) are cyclopeptides in which amide groups are replaced by corresponding lactone bonds due to the presence of a hydroxylated carboxylic acid in the peptide structure. These peptides sometimes display additional chemical modifications, including unusual amino acid residues in their structures. This review highlights the occurrence, structures and biological activities of the fungal CDPs reported until October 2017. About 352 fungal CDPs belonging to the groups of cyclic tri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, deca-, and tridecadepsipeptides have been isolated from fungi. These metabolites are mainly reported from the genera Acremonium, Alternaria, Aspergillus, Beauveria, Fusarium, Isaria, Metarhizium, Penicillium, and Rosellina. They are known to exhibit various biological activities such as cytotoxic, phytotoxic, antimicrobial, antiviral, anthelmintic, insecticidal, antimalarial, antitumoral and enzyme-inhibitory activities. Some CDPs (i.e., PF1022A, enniatins and destruxins) have been applied as pharmaceuticals and agrochemicals.

show abstract

Section: Cyclic Tetradepsipeptidesmentioning

confidence: 99%

Structural Diversity and Biological Activities of Cyclic Depsipeptides from Fungi

et al. 2018

View full text Add to dashboard Cite

show abstract

“…A few cyclodepsipeptides ( Figure 2 ) have also been identified from Cordyceps fungi, e.g., beauveriolide I and III from C. militaris [ 45 ] and beauvericin from C. cicadae [ 23 , 46 ]. Beauveriolides have demonstrated anti-aging [ 47 ], beta-amyloid-lowering [ 48 ], and anti-atherogenic activity by inhibition of lipid droplet accumulation in macrophages without any obvious side effects [ 49 ]. However, insecticidal and nematicidal beauvericin, first isolated from B. bassiana , can induce cytotoxicity and cell apoptosis in a dose-dependent manner due to its ionophoric property that can increase ion permeability in membranes [ 50 ].…”

Section: Known Metabolites Produced By Cordyceps mentioning

confidence: 99%

Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety

Chen

Sun

Luo

et al. 2020

Toxins

View full text Add to dashboard Cite

Ascomycete Cordyceps fungi such as C. militaris, C. cicadae, and C. guangdongensis have been mass produced on artificial media either as food supplements or health additives while the byproducts of culture substrates are largely used as animal feed. The safety concerns associated with the daily consumption of Cordyceps fungi or related products are still being debated. On the one hand, the known compounds from these fungi such as adenosine analogs cordycepin and pentostatin have demonstrated different beneficial or pharmaceutical activities but also dose-dependent cytotoxicities, neurological toxicities and or toxicological effects in humans and animals. On the other hand, the possibility of mycotoxin production by Cordyceps fungi has not been completely ruled out. In contrast to a few metabolites identified, an array of biosynthetic gene clusters (BGCs) are encoded in each genome of these fungi with the potential to produce a plethora of as yet unknown secondary metabolites. Conservation analysis of BGCs suggests that mycotoxin analogs of PR-toxin and trichothecenes might be produced by Cordyceps fungi. Future elucidation of the compounds produced by these functionally unknown BGCs, and in-depth assessments of metabolite bioactivity and chemical safety, will not only facilitate the safe use of Cordyceps fungi as human food or alternative medicine, but will also benefit the use of mass production byproducts as animal feed. To corroborate the long record of use as a traditional medicine, future efforts will also benefit the exploration of Cordyceps fungi for pharmaceutical purposes.

show abstract

“…Different biological and or medicinal activities have been reported for BVD analogs, including antiaging (12), beta-amyloid-lowering (13), and inhibition of acyl-CoA:cholesterol acyltransferase activity to block the synthesis of cholesteryl esters 5 (14,15). The analog of BVDs could be detected in insect hemolymph after B. bassiana infection (16).…”

Section: Abstract Cordycipitaceae Fungi Cyclodepsipeptide Beauveriomentioning

confidence: 99%

Production of diverse beauveriolide analogs in closely related fungi: a rare case of fungal chemodiversity

Yin

Chen

Song

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTFungal chemodiversity is well known in part due to the production of diverse analogous compounds by a single biosynthetic gene cluster (BGCs). Usually, similar metabolites are produced by closely related fungal species. Here we report a rare case of the production of the cyclodepsipeptide beauveriolides (BVDs) in three insect pathogenic fungi. We found that the more closely-related fungi Beauveria bassiana and B. brongniartii produce structurally distinct analogs of BVDs whereas the rather divergently evolved species B. brongniartii and Cordyceps militaris produce structural analogs in a similar pattern. It was verified that a conserved BGC containing four genes is responsible for BVD biosynthesis in three fungi including a polyketide synthase (PKS) for the production of 3-hydroxy fatty acids (FAs) with chain length variations. In contrast to BVD production patterns, phylogenetic analysis of the BGC enzymes or enzyme domains largely resulted in the congruence relationship with fungal speciation. Feeding assays demonstrated that a FA with a chain length of eight carbon atoms was preferentially utilized whereas a FA with a chain longer than 10 carbon atoms could not be used as a substrate for BVD biosynthesis. We also found that addition of D-type amino acids could not enable B. bassiana to produce those analogs biosynthesized by other two fungi. Insect survival assays suggested that the contribution of BVD to fungal virulence might be associated with the susceptibility of insect species. The results of this study enrich the knowledge of fungal secondary metabolic diversity.IMPORTANCEFungal chemotaxonomy is an approach to classify fungi based on fungal production of natural compounds especially the secondary metabolites. We found an atypical example that could question chemical classification of fungi in this study: the more closely-related entomopathogenic species Beauveria bassiana and B. brongniartii produce structurally different analogs of the cyclodepsipeptide beauveriolides whereas the rather divergent species B. brongniartii and Cordyceps militaris biosynthesize similar analogs under the same growth condition. The conserved BGC containing four genes is present in each species and responsible for beauveriolide production. In contrast to the compound formation profiles, the phylogenies of biosynthetic enzymes or enzymatic domains show associations with fungal speciation relationship. Dependent on insect species, production of beauveriolides may contribute to fungal virulence against insect. The findings in this study augment the diversity of fungal secondary metabolisms.

show abstract

Selective inhibition of sterolO-acyltransferase 1 isozyme by beauveriolide III in intact cells

Cited by 21 publications

References 39 publications

Structural Diversity and Biological Activities of Cyclic Depsipeptides from Fungi

Structural Diversity and Biological Activities of Cyclic Depsipeptides from Fungi

Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety

Production of diverse beauveriolide analogs in closely related fungi: a rare case of fungal chemodiversity

Contact Info

Product

Resources

About