Streptomyces hygroscopicus

PURPOSE: Epilepsy is a chronic brain dysfunction characterized by recurrent epileptic seizures. Rapamycin is a naturally occurring macrolide from Streptomyces hygroscopicus, and rapamycin may provide a protective effect on the nervous system by affecting mTOR. Therefore, we investigated the pharmacologic mechanism of rapamycin treating epilepsy through bioinformatics analysis, cellular experiments and supercomputer simulation. METHODS: Bioinformatics analysis was used to analyze targets of rapamycin treating epilepsy...

The largest natural reservoir of untapped carbon can be found in the cell-wall strengthening, plant woody-tissue polymer, lignin - a polymer of catechols or 1,2-dihydroxybenzene monomers. The catecholic carbon of lignin could be valorized into feedstocks and natural products by way of catabolic and biosynthetic transformations, including the oxygen-dependent cleavage reaction of extradiol dioxygenase (EDX) enzymes. The EDX l-DOPA 2,3-dioxygenase was first discovered as part of a biosynthetic gene cluster to the natural product antibiotic, lincomycin, and also contributes to the biosyntheses of anthramycin, sibiromycin, tomaymycin, porothramycin and hormaomycin...

Genome editing tools based on SpCas9 and FnCpf1 have facilitated strain improvements for natural product production and novel drug discovery in Streptomyces . However, due to high toxicity, their editing requires high DNA transformation efficiency, which is unavailable in most streptomycetes. The transformation efficiency of an all-in-one editing tool based on miniature Cas nuclease AsCas12f1 was significantly higher than those of SpCas9 and FnCpf1 in tested streptomycetes, which is due to its small size and weak DNA cleavage activity...

Nigericin, an ionophore derived from Streptomyces hygroscopicus , is arguably the most commonly used tool compound to study the NLRP3 inflammasome. Recent findings, however, showed that nigericin also activates the NLRP1 inflammasome in human keratinocytes. In this study, we resolve the mechanistic basis of nigericin-driven NLRP1 inflammasome activation. In multiple nonhematopoietic cell types, nigericin rapidly and specifically inhibits the elongation stage of the ribosome cycle by depleting cytosolic potassium ions...

MppQ is an enzyme of unknown function from Streptomyces hygroscopicus (ShMppQ) that operates in the biosynthesis of the nonproteinogenic amino acid L-enduracididine (L-End). Since L-End is a component of several peptides showing activity against antibiotic-resistant pathogens, understanding its biosynthetic pathway could facilitate the development of chemoenzymatic routes to novel antibiotics. Herein, we report on the crystal structures of ShMppQ complexed with pyridoxal-5'-phosphate (PLP) and pyridoxamine-5'-phosphate (PMP)...

Alzheimer's disease (AD) is a sporadic or familial neurodegenerative disease of insidious onset with progressive cognitive decline. Although numerous studies have been conducted or are underway on AD, there are still no effective drugs to reverse the pathological features and clinical manifestations of AD. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus . As a classical mechanistic target of rapamycin (mTOR) inhibitor, rapamycin has been shown to be beneficial in a variety of AD mouse and cells models, both before the onset of disease symptoms and the early stage of disease...

In this review article, we present the fascinating story of rapamycin (sirolimus), a drug able to induce γ-globin gene expression and increased production of fetal hemoglobin (HbF) in erythroid cells, including primary erythroid precursor cells (ErPCs) isolated from β-thalassemia patients. For this reason, rapamycin is considered of great interest for the treatment of β-thalassemia. In fact, high levels of HbF are known to be highly beneficial for β-thalassemia patients. The story of rapamycin discovery began in 1964, with METEI, the Medical Expedition to Easter Island (Rapa Nui)...

BACKGROUND: Enhancing rapamycin production using a cost-effective medium is crucial for wider accessibility, reduced manufacturing costs, sustainable pharmaceutical practices, and advancements in therapeutic applications. It promotes global health, biotechnological innovation, research collaboration, and societal well-being through affordable and effective treatments. This study focuses on the development of a novel cost-effective production medium for the synthesis of rapamycin from Streptomyces hygroscopicus...

Geldanamycin is an ansamycin-derivative of a benzoquinone isolated from Streptomyces hygroscopicus. It inhibits tyrosine kinases and heat shock protein 90 (HSP90). Geldanamycin and 11 derivatives were subjected to molecular docking to HSP90, and 17-desmethoxy-17-N,N-dimethylamino-geldanamycin (17-DMAG) was the compound with the highest binding affinity (-7.73 ± 0.12 kcal/mol) and the lowest inhibition constant (2.16 ± 0.49 μM). Therefore, 17-DMAG was selected for further experiments in comparison to geldanamycin...

Fusarium wilt of bananas (FWB) is seriously affecting the sustainable development of the banana industry and is caused by the devastating soil-borne fungus Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4). Biological control is a promising strategy for controlling Fusarium wilt in bananas. We previously identified Streptomyces hygroscopicus subsp. hygroscopicus 5-4 with strong antifungal activity against the FWB. The most possible antimicrobial mechanism of strain 5-4 was explored using the metabolomics approach, light microscopy imaging, and transmission electron microscopy (TEM)...

PURPOSE: The study was conducted to investigate the effectivity and the cytotoxicity of fractions 14 and 36K of metabolite extract of Streptomyces hygroscopicus subsp. Hygroscopicus as an antimalarial compounds against Plasmodium berghei in vitro. METHODS: Fractions 14 and 36K of metabolite extract of Streptomyces hygroscopicus subsp. Hygroscopicus produced by the fractionation process utilizing the Flash Column Chromatography (FCC) BUCHI Reveleris® PREP. Plasmodium berghei culture was used to assess the antimalarial activity of fractions 14 and 36K...

Endophytes play an important role in shaping plant growth and immunity. However, the mechanisms for endophyte-induced disease resistance in host plants remain unclear. Here, we screened and isolated the immunity inducer ShAM1 from the endophyte Streptomyces hygroscopicus OsiSh-2, which strongly antagonizes the pathogen Magnaporthe oryzae. Recombinant ShAM1 can trigger rice immune responses and induce hypersensitive responses in various plant species. After infection with M. oryzae, blast resistance was dramatically improved in ShAM1-inoculated rice...

Extracellular traps are released by neutrophils and other immune cells as part of the innate immune response to combat pathogens. Neutrophil extracellular traps (NETs) consist of a mesh of DNA and histone proteins decorated with various anti-microbial granule proteins, such as elastase and myeloperoxidase (MPO). In addition to their role in innate immunity, NETs are also strongly linked with numerous pathological conditions, including atherosclerosis, sepsis and COVID-19. This has led to significant interest in developing strategies to inhibit NET release...

The advancement in pharmaceutical research has led to the discovery and development of new combinatorial life-saving drugs. Rapamycin is a macrolide compound produced from Streptomyces hygroscopicus. Rapamycin and its derivatives are one of the promising sources of drug with broad spectrum applications in the medical field. In recent times, rapamycin has gained significant attention as of its activity against cytokine storm in COVID-19 patients. Rapamycin and its derivatives have more potency when compared to other prevailing drugs...

Vector control plays a key role in reducing the public health burden of mosquito-borne diseases. Today's vector control strategies largely rely on synthetic insecticides that can have a negative environmental impact when applied outdoors and often become inefficient because of the mosquitoes' ability to develop resistance. An alternative and promising approach to circumvent these challenges involves the implementation of insecticides derived from nature (biopesticides) for vector control. Biopesticides can constitute naturally occurring organisms or substances derived from them that have lifespan-shortening effects on disease vectors such as mosquitoes...

Cholesterol oxidase is a highly demanded enzyme used in medicine, pharmacy, agriculture, chemistry, and biotechnology. It catalyzes oxidation of 3β-hydroxy-5-ene- to 3-keto-4-ene- steroids with the formation of hydrogen peroxide. Here, we expressed 6xHis-tagged mature form of the extracellular cholesterol oxidase (ChO) from the actinobacterium Nocardioides simplex VKM Ac-2033D (55.6 kDa) in Escherichia coli cells. The recombinant enzyme (ChONs ) was purified using affinity chromatography. ChONs proved to be functional towards cholesterol, cholestanol, phytosterol, pregnenolone, and dehydroepiandrosterone...

To investigate the potential for secondary metabolite biosynthesis by Streptomyces species, we employed a coculture method to discover natural bioactive products and identified specific antibacterial activity from a combined-culture of Streptomyces hygroscopicus HOK021 and Tsukamurella pulmonis TP-B0596. Molecular networking using ultrahigh performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) data revealed a specific clade of metabolites in this combined-culture that were not detected in both monocultures...

Trichostatin A (TSA), derived from the bacteria Streptomyces hygroscopicus, is a hydroxamic acid having various biological properties such as histone deacetylase inhibition, anticancer and radiomitigative action. However the mitigative activity of TSA against radiation-induced damages in the mouse reproductive system has not yet been elucidated. The present study unraveled the effects of 2 Gy whole body irradiation (60 Co γ- radiation) on C57BL/6 mice male reproductive system including structural damages to testes, increase in apoptosis and reduction in germ cell viability, reduced fertility as well as increased genomic instability in the next generation...

Introduction: β-thalassemia is caused by autosomal mutations in the β-globin gene, which induce the absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that a high production of fetal hemoglobin (HbF) is beneficial for patients with β-thalassemia. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of Streptomyces hygroscopicus that serves as a strong HbF inducer in vitro and in vivo . In this study, we report biochemical, molecular, and clinical results of a sirolimus-based NCT03877809 clinical trial (a personalized medicine approach for β-thalassemia transfusion-dependent patients: testing sirolimus in a first pilot clinical trial, Sirthalaclin)...

Endophytes can benefit the growth and stress resistance of host plants by secreting bioactive components. Thiamine is an essential vitamin involved in many metabolic pathways and can only be synthesized by microbes and plants. In this study, we found that thiamine could inhibit the development of the phytopathogen Magnaporthe oryzae and decrease the rice blast index under field conditions. In the thiamine biosynthesis pathway, the key enzyme ShTHIC of an endophyte Streptomyces hygroscopicus OsiSh-2 and OsTHIC of rice ( Oryza sativa ) were highly homologous...