Search Results (5)

This research aimed at obtaining new derivatives of pregn-1,4-diene-3,20-dione (Δ¹-progesterone) (2) through microbiological transformation. For the role of catalysts, we used six strains of entomopathogenic filamentous fungi (Beauveria bassiana KCh J1.5, Beauveria caledonica KCh J3.3, Isaria fumosorosea KCh J2, Isaria farinosa KCh KW1.1, Isaria tenuipes MU35, and Metarhizium robertsii MU4). The substrate (2) was obtained by carrying out an enzymatic 1,2-dehydrogenation on an increased scale (3.5 g/L) using a recombinant cholest-4-en-3-one Δ¹-dehydrogenase (AcmB) from Sterolibacterium denitrificans. All selected strains were characterized by the high biotransformation capacity for the used substrate. As a result of the biotransformation, six steroid derivatives were obtained: 11α-hydroxypregn-1,4-diene-3,20-dione (3), 6β,11α-dihydroxypregn-1,4-diene-3,20-dione (4), 6β-hydroxypregn-1,4-diene-3,11,20-trione (5), 6β,17α-dihydroxypregn-1,4-diene-3,20-dione (6), 6β,17β-dihydroxyandrost-1,4-diene-3-one (7), and 12β,17α-dihydroxypregn-1,4-diene-3,20-dione (8). The results show evident variability of the biotransformation process between strains of the tested biocatalysts from different species described as entomopathogenic filamentous fungi. The obtained products were tested in silico using cheminformatics tools for their pharmacokinetic and pharmacodynamic properties, proving their potentially high biological activities. This study showed that the obtained compounds may have applications as effective inhibitors of testosterone 17β-dehydrogenase. Most of the obtained products should, also with a high probability, find potential uses as androgen antagonists, a prostate as well as menopausal disorders treatment. They should also demonstrate immunosuppressive, erythropoiesis-stimulating, and anti-inflammatory properties. Full article

The content of bounded amino acids in six entomopathogenic fungi was identified and determined. Analyzing the elements characterizing the pathogenicity of individual species of fungi based on infectivity criteria, ranges of infected hosts, and the ability to induce epizootics, these can be ranked in the following order: Isaria farinosa, Isaria tenuipes, Isaria fumosorose, Lecanicillium lecanii, Conidiobolus coronatus, Isaria coleopterorum. These fungi represent two types of Hyphomycetales-Paecilomyces Bainier and Verticillium Nees ex Fr. and one type of Entomophtorales-Conidiobolus Brefeld. Our study indicates that there are significant quantitative and qualitative differences of bounded amino acids in the entomopathogenic fungal strains contained in the mycelium between high and low pathogenicity strains. The richest composition of bounded amino acids has been shown in the mycelium of the Isaria farinosa strain, which is one of the most commonly presented pathogenic fungi in this group with a very wide range of infected hosts and is the most frequently recorded in nature as an important factor limiting the population of insects. Full article

The present investigation aimed to determine the fungal toxicity of Isaria tenuipes (My-It) against the dengue mosquito vector Aedes aegypti L. and its non-target impact against the aquatic predator Toxorhynchitessplendens. Lethal concentrations (LC₅₀ and LC₉₀) of My-It were observed in 2.27 and 2.93 log ppm dosages, respectively. The sub-lethal dosage (My-It-1 × 10⁴ conidia/mL) displayed a significant oviposition deterrence index and also blocked the fecundity rate of dengue mosquitos in a dose-dependent manner. The level of major detoxifying enzymes, such as carboxylesterase (α-and β-) and SOD, significantly declined in both third and fourth instar larvae at the maximum dosage of My-It 1 × 10⁵ conidia/mL. However, the level of glutathione S-transferase (GST) and cytochrome P-450 (CYP450) declined steadily when the sub-lethal dosage was increased and attained maximum reduction in the enzyme level at the dosage of My-It (1 × 10⁵ conidia/mL). Correspondingly, the gut-histology and photomicrography results made evident that My-It (1 × 10⁵ conidia/mL) heavily damaged the internal gut cells and external physiology of the dengue larvae compared to the control. Moreover, the non-target toxicity against the beneficial predator revealed that My-It at the maximum dosage (1 × 10²⁰ conidia/mL) was found to be less toxic with <45% larval toxicity against Tx.splendens. Thus, the present toxicological research on Isaria tenuipes showed that it is target-specific and a potential agent for managing medically threatening arthropods. Full article

Accurate detection and differentiation of adulterants in food ingredients and herbal medicines are crucial for the safety and basic quality control of these products. Ophiocordyceps sinensis is described as the only fungal source for the authentic medicinal ingredient used in the herbal medicine “Cordyceps”, and two other fungal species, Cordyceps militaris and Isaria tenuipes, are the authentic fungal sources for food ingredients in Korea. However, substitution of these three species, and adulteration of herbal material and dietary supplements originating from Cordyceps pruinosa or Isaria cicadae, seriously affects the safety and reduces the therapeutic efficacy of these products. Distinguishing between these species based on their morphological features is very difficult, especially in commercially processed products. In this study, we employed DNA barcode-based species-specific sequence characterized amplified region (SCAR) markers to discriminate authentic herbal Cordyceps medicines and Cordyceps-derived dietary supplements from related but inauthentic species. The reliable authentication tool exploited the internal transcribed spacer (ITS) region of a nuclear ribosomal RNA gene (nrDNA). We used comparative nrDNA-ITS sequence analysis of the five fungal species to design two sets of SCAR markers. Furthermore, we used a set of species-specific SCAR markers to establish a real-time polymerase chain reaction (PCR) assay for the detection of species, contamination, and degree of adulteration. We confirmed the discriminability and reproducibility of the SCAR marker analysis and the real-time PCR assay using commercially processed food ingredients and herbal medicines. The developed SCAR markers may be used to efficiently differentiate authentic material from their related adulterants on a species level. The ITS-based SCAR markers and the real-time PCR assay constitute a useful genetic tool for preventing the adulteration of Cordyceps and Cordyceps-related dietary supplements. Full article

Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Therefore, small molecular inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes diseases. In a continuing search for new protein phosphatase inhibitors from fungi, we have isolated a new compound, named penostatin J (1), together with three known ones, penostatin C (2), penostatin A (3), and penostatin B (4), from cultures of the entomogenous fungus Isaria tenuipes. The structure of penostatin J (1) was elucidated by extensive spectroscopic analysis. We also demonstrate for the first time that penostatin derivatives exhibit the best PTP1B inhibitory action. These findings suggest that penostatin derivatives are a potential novel kind of PTP1B inhibitors. Full article