Publications by authors named "Takuji Nakashima"

Nanaomycin K is a natural compound found in the culture broth of "Streptomyces rosa subsp. notoensis" OS-3966. Studies have shown that it inhibits epithelial-mesenchymal transition (EMT), a recognized mechanism of cancer cell migration.

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Since the discovery of penicillin, a vast array of microbial antibiotics has been identified and applied in the medical field. Globally, the search for drug candidates microbial screening is ongoing. Traditional screening methods, however, are time-consuming and require labor-intensive sample processing, significantly reducing throughput.

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  • - A new physicochemical screening method using d-Ala-d-Ala silica gel led to the discovery of two macrolactams, banglactams A and B, from the K18-0086 culture broth.
  • - The d-Ala-d-Ala silica gel effectively differentiated and separated the banglactams, but the instability and insolubility of one prevented structural elucidation initially.
  • - By chemically modifying the unstable compound, researchers improved its solubility, allowing for further study, and found that banglactams exhibited antibacterial activity when bound to the silica gel.
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Two new pramanicin analogs, named virgaricins C (1) and D (2), were discovered by physicochemical screening from a static cultured material of Apiospora sp. FKI-8058. Their structures were elucidated by MS and NMR analyses and chemical derivatization.

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Vancomycin is a potent and broad-spectrum antibiotic that binds to the d-Ala-d-Ala moiety of the growing bacterial cell wall and kills bacteria. This fascinating binding model prompted us to design and synthesize d-Ala-d-Ala silica gels for the establishment of a new physicochemical (PC) screening method. In this report, we confirmed that vancomycin binds to d-Ala-d-Ala silica gel and can be eluted with MeOH containing 50 mM TFA.

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  • * Experiments demonstrate that nanaomycin K significantly inhibits cell proliferation and tumor growth, both in vitro and in vivo, particularly in TRAMP-C2 carcinoma-bearing mice.
  • * The drug's mechanism involves the suppression of processes like epithelial-mesenchymal transition and the MAPK signaling pathway, leading to reduced tumor migration and enhanced apoptosis markers.
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Streptomyces avermitilis is a gram-positive bacterium that undergoes complex physiological and morphological differentiation during its life cycle, which has implications in secondary metabolite production. Avermectin, produced by S. avermitilis, is widely used as an anthelmintic and insecticidal agent.

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The nitrogen rule in mass spectrometry was used to search for new nitrogen-compounds from microbial metabolites. During this program, two new nitrogen-containing compounds, penicidones E and F, were discovered from the filamentous fungal strain FKI-7498, which was isolated from soil collected in Tokushima, Japan, and identified as Oidiodendron sp. by sequence analysis of the internal transcribed spacer region, including 5.

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Many useful natural products are usually screened based on their biological activities. On the other hand, various natural products can be detected based on their physicochemical properties. We have already reported the isolation and characterization of mangromicins from a cultural broth of Lechevalieria aerocolonigenes K10-0216 using physicochemical screening.

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  • * It exhibits antibacterial activity specifically against Gram-positive bacteria and has cytotoxic effects on human cancer cell lines.
  • * Researchers have proposed a biosynthetic pathway for sattahipmycin using genomic data, which involves a newly identified type II polyketide synthase gene cluster.
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The mechanism of production of extracellular vesicles (EVs) and their molecular contents are of great interest due to their diverse roles in biological systems and are far from being completely understood. Even though cellular cargo releases mediated by EVs have been demonstrated in several cases, their role in secondary metabolite production and release remains elusive. In this study, this aspect is investigated in detail using Raman microspectroscopic imaging.

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Trehangelins (THG) are newly identified trehalose compounds derived from broth cultures of an endophytic actinomycete, Polymorphospora rubra. THG are known to suppress Cellular Communication Network factor 1 (CCN1), which regulates collagen homeostasis in the dermis. Although the physical properties of THG suggest a high penetration of the stratum corneum, the effect of THG on the epidermis has not been reported.

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  • - The actinomycete strain LCR2-06, isolated from lichen in Thailand, displays growth at temperatures between 25-45°C and a pH range of 6-11, and is characterized by specific cellular components like -diaminopimelic acid and a unique sugar profile.
  • - Genomic analysis shows that LCR2-06 has an 11.1 Mb draft genome with a 72.7 mol% G+C content, demonstrating high genetic similarity to other strains, as indicated by ANIb and ANIm values of 90.0% and 92.0%, respectively.
  • - Strain LCR2-06 produces an antibacterial compound effective against certain bacterial strains and is
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Indolizidine alkaloids, which have versatile bioactivities, are produced by various organisms. Although the biosynthesis of some indolizidine alkaloids has been studied, the enzymatic machinery for their biosynthesis in Streptomyces remains elusive. Here, we report the identification and analysis of the biosynthetic gene cluster for iminimycin, an indolizidine alkaloid with a 6-5-3 tricyclic system containing an iminium cation from Streptomyces griseus.

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Nanaomycin K, derived from Streptomyces rosa subsp. notoensis OS-3966, has been discovered to have inhibitory bioactivity on epithelial-mesenchymal transition (EMT), an important mechanism of cancer cell invasion and migration. In this study, we examined the anti-EMT and anti-tumor effect of nanaomycin K in bladder cancer, where EMT has important roles in progression.

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An anti-mannheimiosis agent, aldsulfin, was isolated from a culture broth of the fungus Lasiodiplodia pseudotheobromae FKI-4499, together with a known compound, lasiodipline C, using bioassay-guided fractionation. Spectroscopic analysis of aldsulfin, using NMR, mass spectrometry, and CD analyses revealed it to be an epithiodiketopiperazine with an unstable and unusual hemithioaminal moiety. Aldsulfin showed antibacterial activity against Mannheimia haemolytica and Pasteurella multocida.

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  • Raman spectroscopy is a technique used for chemical identification due to its sensitivity to molecular structures, and the rise of handheld and smartphone devices is making it accessible to less trained users.
  • The quality of Raman spectra can vary due to factors like signal-to-noise ratio and background fluctuations, making it challenging to achieve a perfect match with existing spectral libraries.
  • This manuscript examines the impact of these variations on spectral matching results and highlights the need for careful consideration in developing spectral libraries to improve accuracy in applications across various fields.
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  • Raman microspectroscopy is a technique that identifies molecules without the need for labeling, allowing for minimally invasive analysis.
  • The study successfully detected penicillin G within KF425 fungal cells using advanced analysis methods to separate overlapping spectral signatures of various molecular components.
  • This approach not only maps the presence of proteins and lipids but also pinpoints where penicillin G is located within the cells, suggesting its use for screening bioactive compounds in microorganisms.
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Two new nitrogen-containing metabolites, designated hatsusamide A () and B (), were isolated from a culture broth of FKJ-0213 together with the known compounds tanzawaic acid B () and trichodermamide C () by physicochemical (PC) screening. The structures of and were determined as a tanzawaic acid B-trichodermamide C hybrid structure and a new analog of aspergillazines, respectively. The absolute configuration of was determined by comparing the values of tanzawaic acid B and trichodermamide C in the literatures, such as H-nuclear magnetic resonance (H-NMR) data and optical rotation, after hydrolysis of .

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The present study investigated whether or not the oral administration of trehangelin-A (THG-A) is effective for metabolic disorders caused by a high-fat diet, as we previously showed that the intraperitoneal administration of THG-A improved metabolic disorders caused by a high-fat diet. Mice received a control diet or high-fat diet for eight weeks. Concurrently, mice were orally administered 0.

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Two new sulfur compounds, designated thioporidiol A () and B (), were discovered by the MoS-screening program from a culture broth of FKI-7382. The structures of and were determined as C13 lipid structures with an -acetylcysteine moiety. The relative configuration at the C-5 and C-6 position of was determined by the derivatives of -methoxy--phenylacetic acid diesters, and the absolute configuration of the -acetylcysteine moiety was determined by advanced Marfey's analysis.

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The molybdenum (Mo)-catalyzed oxidation of sulfide under neutral conditions yields sulfone. This reaction proceeds more smoothly than olefin epoxidation and primary or secondary alcohol oxidation. In this study, Mo-catalyzed oxidation was used to screen for sulfur compounds (named "MoS-screening") in microbial broths by liquid chromatography-mass spectrometry (LC/MS).

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A new nitrogen-containing compound, trichothioneic acid, was discovered from the metabolites of fungal strain FKI-7573 using a mass spectrometry screening method guided by odd number of molecular weights, which indicates compounds that contain an odd number of nitrogen atoms. Strain FKI-7573 was isolated from soil collected in Obihiro, Hokkaido, Japan, and identified as Trichoderma virens by a sequence analysis of the internal transcribed spacer region, including 5.8S ribosomal RNA.

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  • This study investigates the effectiveness of trehangelin A (THG-A) for treating metabolic conditions induced by high-fat diets in mice.
  • Mice on a high-fat diet showed increased body weight and unhealthy serum levels, while THG-A treatment significantly reduced triglycerides and glucose levels, and improved HDL-C and adiponectin levels.
  • THG-A also suppressed pro-inflammatory markers associated with high-fat diet-induced obesity, suggesting its potential as a therapeutic option for obesity-related metabolic disorders.
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A new chaetochiversin analog, designated chaetochiversin C (1), was discovered from a cultured broth of fungal strain FKI-7792 by physicochemical screening. This strain was identified as a member of genus Neocosmospora based on morphology and DNA barcoding. The partially relative configuration of 1 was determined by C-NMR chemical shifts of the acetonide analog of 1.

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