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Кристальная структура и каталитический механизм дрименоловой синтазы, необычная двухфункциональная терпеновая киклаза-фосфатаза.

Дрименол синтаза из Aquimarina pongiae (ASDMS) — очень необычная химера, интегрирующая two - отдельные, последовательные операции по переработке изопреноидов в рамках единой полипептидной цепи. ASDMS катализирует циклизацию фарнесилового дифосфата (FPP) класса II для образования дрименилового дифосфата, который затем подвергается гидролизу энзим-катализу для получения дрименинола, биоактивного сескитерпенового спирта с антифунгальными и антираковыми свойствами. Здесь мы сообщаем рентгеновские кристаллы ASDMS и его комплекс с сескитерпен тиол. Структура ASDMS имеет дидомаиновую архитектуру, сос

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… Discussion It is instructive to compare the structure of AsDMS with that of the recently reported drimenyl diphosphate synthase from Streptomyces showdoensis (SsDMS) ( 33 ). … W., Structure of epi -isozizaene synthase from Streptomyces coelicolor A3(2), a platform for new terpenoid cyclization templates. Biochemistry 49, 1787–1797 (2010). 46. Allen K. N., Dunaway-Mariano D., Markers of fitness in a successful enzyme superfamily. Curr. Opin. Struct. …

Narrative Review of Drug-Associated Nail Toxicities in Oncologic Patients.

IntroductionNail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy.ObjectivesWe aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management.MethodsRetrieved literature from PubMed regis

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… Antitumor antibiotics Anthracyclines: Doxorubicin and Daunorubicin The anthracyclines doxorubicin and daunorubicin are derived from the bacterium Streptomyces peucetius var. caesius and are used to treat various hematologic malignancies and solid tumors. … Bleomycin Bleomycin is a glycopeptide produced by the bacterium Streptomyces verticillus and is used for the treatment of squamous cell carcinoma, lymphoma, testicular carcinoma, and malignant pleural effusion. …

Адаптация эукариот-подобных PRS к прокариот-подобным tRNAPro.

Синтеты Проли-ТРНА (ПРОРС) уникальны среди аминоачил-тРНК (ААРС) two различные структурные архитектуры различных организмов: прокариота-подобные (П-тип) и эукариоте/археон-подобные (Е-тип). Интересно, что Бакиллус Тюрингьенси гавань обоих типов, сосуществует P-тип (BtProRS1) и E-тип PRS (BtProRS2). Несмотря на свои различия, оба фермента формально выражаются и функционируют в vivo. По аналогии с BtProRS1, BtPRS2 выборочно заряжает TRNAPro типа P и демонстрирует более высокий допуск к галоугинону, чем каноническая PRS. Однако эти two Изозимы признают основные идентификационные элементы типа P t

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… Cispentacin, produced by Bacillus cereus L450-B2 and Streptomyces setonii No. 7562, shares structural similarities with proline and exhibits moderate efficacy in inhibiting fungal ProRS as an antifungal agent ( 50 ). … On the other hand, phosmidosine, produced by the soil bacteria Streptomyces sp., resembles proline-AMP and shows inhibitory effects on tumor growth ( 51 , 52 ). …

Tatami Mats: A Source of Pitted Keratolysis in a Martial Arts Athlete?

Dear Editor, Pitted keratolysis (PK), also known as keratosis plantaris sulcatum, is a non-inflammatory, bacterial, superficial cutaneous in … bacterium species, Kytococcus sedentarius, Dermatophilus congolensis, Actynomices keratolytica, and Streptomyces that proliferate and produce proteinase and sulfur-compound by-products under appropriate moist conditions (5-7). Proteinases digest the keratin and destroy the stratum corneum, producing the characteristic skin findings, while sulfur compounds (sul …

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are sti

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… The first group of molecules of the class were obtained from Streptomyces aureofaciens and Streptomyces rimosus , respectively, but the most recently discovered molecules are semisynthetic [ 22 ]. Macrolides were originally isolated from Streptomyces species. …

Liposomal Drug Delivery Systems and Anticancer Drugs.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredien

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… DOX is an anthracycline antibiotic (isolated from Streptomyces peucetius var. caesius ) with potent anticancer activity that is widely used in the treatment of solid and hematologic neoplasms (such as breast cancer and lymphoma) [ 93 ]. … Daunorubicin (DNR) is another anthracycline antibiotic (isolated from Streptomyces peucetius varcaesitue ) drug with anticancer activity [ 97 ]. …

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, m

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… Strains of Streptomyces bacteria such as Streptomyces corchorusii subspecies rhodomarinus presented fascinating antidiabetic properties by inhibiting the activity of enzyme amylase, while other species of a similar strain led to the production of two novel compounds having N-acetyl-glucosaminidase inhibition …

Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19.

BackgroundGlomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.SummaryThe advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However,

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… Of note, these classes of compounds derive from microorganisms (e.g., cyclosporin(e) from the fungus Tolypocladium inflatum ; tacrolimus from the bacterium Streptomyces tsukubaensis ; and sirolimus from the bacterium Streptomyces hygroscopicus ) that apparently evolved them to modulate the immune system …

Естественные и синтетические АМП из Латинской Америки по всему спектру технологий и приложений в области разнообразия.

Биоразнообразие в Латинской Америке примерно 60% в целом по миру, подпитывая научные исследования в области природных продуктов, весьма значимой области открытия наркотиков по сей день. Это сопровождается увеличением числа антимикробных пептидов (АМП), полученных из натуральных продуктов в регионе, которые за последнее десятилетие были переработаны путем модификации, усовершенствования и уточнения их физико-химических свойств и антимикробной эффективности с использованием подходов, которые варьируются от изучения рациональной конструкции и соотношения структуры-активности (САР) до методов иску

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… H-KF8 | L3 | NRPs | 698.4 | W D A D V D AW-Orn-T-Orn- D V-Y(NO 2 )-K-NH 2 | 90–350 | Streptomyces sp. … For instance, marine-derived Streptomyces sp. H-KF8 strains isolated from Chilean Patagonia have been shown, through genome mining and experimental validation, to produce NRPs with antimicrobial activity, including cyclic peptides with membrane-targeting mechanisms. …

Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting p

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… Cytotrienin A and Ansatrienin B Cytotrienin A (Cyt A) is a natural ansamycin compound derived from Streptomyces sp. with potent anticancer activity [ 66 ]. … BE-43547A 2 The natural product BE-43547A 2 was originally isolated from the Streptomyces sp. strain A43547. …

Recent Progress in CDK4/6 Inhibitors and PROTACs.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based

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… Staurosporie ( 81 , Figure 16 ), an alkaloid from the Streptomyces strain, shows potent CDK4 inhibition activity with an IC 50 value of 59 nM [ 88 , 89 ]. In 1994, L. M. … X-ray structure of staurosporine: A new alkaloid from a Streptomyces strain J. Chem. Soc. Chem. Commun. 1978 18 800 10.1039/C39780000800 89. Sanchez-Martinez C. Shih C. Faul M.M. Zhu G. Paal M. Somoza C. Li T. Kumrich C.A. Winneroski L.L. Xun Z. …

Molecular Inhibitors of Growth Signals

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… Sirolimus (rapamycin) was first discovered in the 1970s as a product of the bacterium Streptomyces hygroscopicus, present in a soil sample from Easter Island (Rapa Nui). The name of the compound was derived from that island. …

Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

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… Actinomycin D [ 88 ] and Bleomycin [ 89 ], derived from Actinomyces and Streptomyces species, cause DNA damage through intercalation and free radical generation, targeting cancers such as sarcomas and ovarian carcinomas. … 88 ] Bleomycin | – | Several cell lines | Hodgkin’s disease, non-Hodgkin’s lymphoma, testicular carcinomas, ovarian cancer, malignant pleural effusion | Bleomycin (BLM) binds to DNA and Fe(II), generates hydroxyl radicals which induce DNA cleavage and cause Fe(II) to oxidize, leading to DNA damage | Streptomyces …

Alkylating anticancer agents and their relations to microRNAs.

Alkylating agents represent an important class of anticancer drugs. The occurrence and emergence of tumor resistance to the treatment with alkylating agents denotes a severe problem in the clinics. A detailed understanding of the mechanisms of activity of alkylating drugs is essential in order to overcome drug resistance. In particular, the role of non-coding microRNAs concerning alkylating drug activity and resistance in various cancers is highlighted in this review. Both synthetic and natural alkylating agents, which are approved for cancer therapy, are discussed concerning their interplay w

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… The first mitomycins A and B were isolated in 1956 before mitomycin C was obtained as blue-violet crystals from Streptomyces caespitosus by Japanese groups in 1958 [ 116 , 117 ] . … Cancer Treat Rev 1976 3 121 39 10.1016/S0305-7372(76)80019-9 786455 116 Hata T Sugawara R Mitomycin, a new antibiotic from Streptomyces. II. Description of the strain. …

Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation.

Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis. Several immune modulatory oligonucleotides and small molecular weight compounds, incl

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… Antrodia cinnamomea extract | Natural ( A. cinnamomea product) | Inhibit cytokine expression Curcumin | Natural (grapes product) | Inhibit NF- κ B activation and cytokine expression Resveratrol | Natural (grapes product) | Inhibit NF- κ B activation and cytokine expression Thiostrepton | Natural ( Streptomyces … product) | Inhibits endosomal acidification and proteasomal activity Azithromycin | Natural ( Streptomyces product) | Inhibits endosomal acidification and proteasomal activity Andrographolide | Natural ( A. paniculata product) | Promotes downregulation of myD88 6.1. …

Amelioration of severe TNBS induced colitis by novel AP-1 and NF- κ B inhibitors in rats.

AP-1 and NF-κ B inhibitors, namely, DTCM-G and DHMEQ, were investigated in male Wistar rats with severe colitis, induced by TNBS. The animals were randomized into 3 groups. The control group received 0.5 mL of 0.5% of the vehicle i.p., the DTCM-G group received 22.5 mg/kg body weight DTCM-G in 0.5% i.p., and the DHMEQ group received 15 mg/kg body weight DHMEQ i.p., all twice daily for 5 days. The body weight losses and mortality rates were significantly higher in the control group than those in DTCM-G-treated and DHMEQ-treated groups. The endoscopic inflammation scores in the control, DTCM-G-t

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… The piperidine compound 9-methylstreptimidone has been isolated from Streptomyces sp. [ 14 ]. 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G) is a synthetic derivative of 9-methylstreptimidone that has been shown to possess potent anti-inflammatory activity in animal experiments [ 15 ]. …

Biomaterials from the sea: Future building blocks for biomedical applications.

Marine resources have tremendous potential for developing high-value biomaterials. The last decade has seen an increasing number of biomaterials that originate from marine organisms. This field is rapidly evolving. Marine biomaterials experience several periods of discovery and development ranging from coralline bone graft to polysaccharide-based biomaterials. The latter are represented by chitin and chitosan, marine-derived collagen, and composites of different organisms of marine origin. The diversity of marine natural products, their properties and applications are discussed thoroughly in t

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… Hydrolase Degrade chitin and chitosan [ [164] , [165] , [166] ] Alginate lyases Algae marine invertebrates Vibrio splendidus 12B01 Lyases Degrade alginate [ [167] , [168] , [169] ] Agarases Cytophaga Bacillus Vibrio Alteromonas Pseudoalteromonas Streptomyces Vibrio sp. … YS-80-122 | Hydrolase | Degrade carrageenans | [ [172] , [173] , [174] , [175] ] Cellulose and hemicellulose hydrolase | Cytophaga, Cellulomonas, Vibrio, Clostridium, Streptomyces Fusarium, Chaetomium, Phoma, Sporotrichum, Glaciecola sp. strain 4H-3–7+YE-5 | Hydrolase | Break down cellulose | [ [176] …

The roles of microRNA families in hepatic fibrosis.

The Japan-China Joint Medical Workshop on Drug Discoveries and Therapeutics 2008 (JCMWDDT 2008) was held from September 29 to October 1, 200 … unji Inokoshi (Kitasato University, Japan) ● Nosokomycins, novel anti-MRSA antibiotics, produced by Streptomyces sp. K04-0144 by OR. Uchida (Kitasato University, Japan) ● In vivo screening for antimicrobial activity of Thai Herbal Medicines using silkworm model by Santad Chanprapaph (Chulalongkorn University, Thailand) ● Novel electrochemical sensor of nitric …

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

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… Salinomycin Salinomycin, an anti‐bacterial polyether isolated from Streptomyces albus , selectively eliminated CD133 + cells in CRC [ 76 ]. … Rapamycin Rapamycin, a macrolide from Streptomyces hygroscopicus , is clinically used due to its immunosuppressant functions. It is a known mTOR inhibitor. Interestingly, rapamycin treatment decreased the spheroid‐forming ability and ALDH1 activity in CRC Caco‐2 and SW480 cell lines [ 211 ]. …

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy reg

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… These developments could be attributed, in part, to chemotherapeutics such as doxorubicin (DOX), an anthracycline antibiotic initially discovered from Streptomyces peucetius . … Doxorubicin and daunorubicin are cytostatic anthracyclines that were discovered in fungi of the genus streptomyces. Doxorubicin exhibits a broad range of activity against both solid tumors and hematological malignancies. …