Pub Date : 2025-08-15DOI: 10.1038/s41429-025-00856-1
Edgar Augusto Ortiz-Benitez, Diego Jeovani Huerta-Flores, Norma Velázquez-Guadarrama, Marco Antonio González-López, José de Jesús Olivares-Trejo
Streptococcus pneumoniae (S. pneumoniae) is a leading cause of respiratory infections, with increasing antibiotic resistance posing a major challenge. While gold nanoparticles (AuNPs) functionalised with antibiotics have been explored, their impact on bacterial adherence and invasion remains underexplored. This study presents a vancomycin-conjugated AuNP formulation designed to enhance antibacterial efficacy and prevent S. pneumoniae colonisation. The nano-formulation was characterised using UV-Vis spectroscopy and TEM, confirming successful conjugation and a uniform spherical size of 23 ± 1 nm. Minimum inhibitory concentration (MIC) assays demonstrated a significant reduction in the required concentrations of AuNPs (from 512 to 32 µg ml-1) and vancomycin (from 0.5 to 0.125 µg ml-1) compared to their individual use. Unlike previous studies that focused solely on bacterial viability, our work demonstrates that the nano-antibiotic effectively inhibits bacterial adherence and invasion in human alveolar epithelial cells (A549). Mechanistically, vancomycin weakens the bacterial cell wall, facilitating AuNP penetration, membrane disruption, and oxidative stress-induced bacterial death. This dual-action mechanism not only enhances bactericidal effects but also prevents bacterial colonisation—an aspect not extensively explored in prior studies. Toxicity assays confirmed that the formulation was non-toxic to A549 cells, supporting its potential for clinical applications. These findings highlight the synergistic antibacterial and anti-infective properties of vancomycin-functionalised AuNPs, offering a promising strategy to combat S. pneumoniae infections while mitigating antibiotic resistance.
{"title":"Gold nanoparticles functionalised with vancomycin enhance antibacterial activity and inhibit Streptococcus pneumoniae adherence and invasion in alveolar cells","authors":"Edgar Augusto Ortiz-Benitez, Diego Jeovani Huerta-Flores, Norma Velázquez-Guadarrama, Marco Antonio González-López, José de Jesús Olivares-Trejo","doi":"10.1038/s41429-025-00856-1","DOIUrl":"10.1038/s41429-025-00856-1","url":null,"abstract":"Streptococcus pneumoniae (S. pneumoniae) is a leading cause of respiratory infections, with increasing antibiotic resistance posing a major challenge. While gold nanoparticles (AuNPs) functionalised with antibiotics have been explored, their impact on bacterial adherence and invasion remains underexplored. This study presents a vancomycin-conjugated AuNP formulation designed to enhance antibacterial efficacy and prevent S. pneumoniae colonisation. The nano-formulation was characterised using UV-Vis spectroscopy and TEM, confirming successful conjugation and a uniform spherical size of 23 ± 1 nm. Minimum inhibitory concentration (MIC) assays demonstrated a significant reduction in the required concentrations of AuNPs (from 512 to 32 µg ml-1) and vancomycin (from 0.5 to 0.125 µg ml-1) compared to their individual use. Unlike previous studies that focused solely on bacterial viability, our work demonstrates that the nano-antibiotic effectively inhibits bacterial adherence and invasion in human alveolar epithelial cells (A549). Mechanistically, vancomycin weakens the bacterial cell wall, facilitating AuNP penetration, membrane disruption, and oxidative stress-induced bacterial death. This dual-action mechanism not only enhances bactericidal effects but also prevents bacterial colonisation—an aspect not extensively explored in prior studies. Toxicity assays confirmed that the formulation was non-toxic to A549 cells, supporting its potential for clinical applications. These findings highlight the synergistic antibacterial and anti-infective properties of vancomycin-functionalised AuNPs, offering a promising strategy to combat S. pneumoniae infections while mitigating antibiotic resistance.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 11","pages":"674-685"},"PeriodicalIF":2.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical studies of Gandjariella species from geothermal soil led to the isolation of three new glycosylated anthracyclines, mutactimycins H−J (1−3), along with known mutactimycin E (4). The structures of 1−3 were elucidated by combination of spectroscopic analyses and chemical degradation. Compounds 1−4 exhibited antibacterial activity against four Mycobacterium species with MIC values ranging from 3.13 to 50 μg mL−1.
{"title":"Mutactimycins H–J, antimycobacterial anthracyclines, from a thermophilic actinomycete of the genus Gandjariella","authors":"Desy Wulan Triningsih, Satsuki Kimachi, Fitria Ningsih, Wellyzar Sjamsuridzal, Satoru Shigeno, Elyza Aiman Azizah Nur, Taichi Ohshiro, Yasuhiro Igarashi","doi":"10.1038/s41429-025-00858-z","DOIUrl":"10.1038/s41429-025-00858-z","url":null,"abstract":"Chemical studies of Gandjariella species from geothermal soil led to the isolation of three new glycosylated anthracyclines, mutactimycins H−J (1−3), along with known mutactimycin E (4). The structures of 1−3 were elucidated by combination of spectroscopic analyses and chemical degradation. Compounds 1−4 exhibited antibacterial activity against four Mycobacterium species with MIC values ranging from 3.13 to 50 μg mL−1.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 11","pages":"651-658"},"PeriodicalIF":2.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-12DOI: 10.1038/s41429-025-00857-0
Rongjian Gao, Yazi Chen, Yan Xiao, Jian Gao
A novel actinobacterium strain cg36T, from the rhizosphere of Cyclosorus parasiticus, was subjected to a polyphasic taxonomic study. 16S rRNA gene sequence analysis showed that strain cg36T shared the highest 16S rRNA gene sequence similarity to Streptomyces lavendofoliae NBRC 12882T. Phylogenetic analysis of 16S rRNA gene sequence indicated that strain cg36T formed a distinct branch within the genus Streptomyces. Phylogenetic analysis of five housekeeping gene and whole genome sequences showed that strain cg36T was closely related to Streptomyces crystallinus JCM 5067T and Streptomyces noboritoensis JCM 4557T. But, overall genome related index (OGRI) and multilocus sequence analysis (MLSA) confirmed that strain cg36T was clearly different from them. A comparison of differential features among strain cg36T, S. crystallinus CGMCC 4.1600T and S. noboritoensis CGMCC 4.1457T provided, at least to some extent, some useful information for strain cg36T as an independent species. In addition, OGRI values and MLSA evolutionary distance between strain cg36T and other strains, which had 16S rRNA gene sequence similarity of >98.65% to strain cg36T, further demonstrated that strain cg36T was a new species. Whole-cell hydrolysates of strain cg36T contained ll-diaminopimelic acid and whole-cell sugars contain glucose. The predominant cellular fatty acids (>10%) were anteiso-C15:0, iso-C15:0 and C16:0. The DNA G + C content of the genome sequence, consisting of 9,022,416 bp, was 72.5%. All these data indicated that strain cg36T represents a novel Streptomyces species, for which the name Streptomyces cyclosori sp. nov. is proposed. The type strain is strain cg36T (=MCCC 1K09286T = JCM 37520T).
{"title":"Streptomyces cyclosori sp. nov., a novel actinobacterium from the rhizosphere soil of Cyclosorus parasiticus (L.) Farw","authors":"Rongjian Gao, Yazi Chen, Yan Xiao, Jian Gao","doi":"10.1038/s41429-025-00857-0","DOIUrl":"10.1038/s41429-025-00857-0","url":null,"abstract":"A novel actinobacterium strain cg36T, from the rhizosphere of Cyclosorus parasiticus, was subjected to a polyphasic taxonomic study. 16S rRNA gene sequence analysis showed that strain cg36T shared the highest 16S rRNA gene sequence similarity to Streptomyces lavendofoliae NBRC 12882T. Phylogenetic analysis of 16S rRNA gene sequence indicated that strain cg36T formed a distinct branch within the genus Streptomyces. Phylogenetic analysis of five housekeeping gene and whole genome sequences showed that strain cg36T was closely related to Streptomyces crystallinus JCM 5067T and Streptomyces noboritoensis JCM 4557T. But, overall genome related index (OGRI) and multilocus sequence analysis (MLSA) confirmed that strain cg36T was clearly different from them. A comparison of differential features among strain cg36T, S. crystallinus CGMCC 4.1600T and S. noboritoensis CGMCC 4.1457T provided, at least to some extent, some useful information for strain cg36T as an independent species. In addition, OGRI values and MLSA evolutionary distance between strain cg36T and other strains, which had 16S rRNA gene sequence similarity of >98.65% to strain cg36T, further demonstrated that strain cg36T was a new species. Whole-cell hydrolysates of strain cg36T contained ll-diaminopimelic acid and whole-cell sugars contain glucose. The predominant cellular fatty acids (>10%) were anteiso-C15:0, iso-C15:0 and C16:0. The DNA G + C content of the genome sequence, consisting of 9,022,416 bp, was 72.5%. All these data indicated that strain cg36T represents a novel Streptomyces species, for which the name Streptomyces cyclosori sp. nov. is proposed. The type strain is strain cg36T (=MCCC 1K09286T = JCM 37520T).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 11","pages":"666-673"},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07DOI: 10.1038/s41429-025-00859-y
Jiahui Li, Zheng Zhou, Qiaoling Zhou
Alcoholic fatty liver disease (AFLD) is a type of liver damage caused by excessive alcohol consumption. Kaempferol (Kae) has been shown to have good anti-cancer effects. This study aimed to investigate the effect and the mechanism of Kae on AFLD at the cellular level. THLE-2 cells were treated with ethanol to establish an AFLD cell model. The effect of Kae on lipid accumulation was assessed through the level of intracellular triglyceride (TG), intracellular total cholesterol (TC), cellular lipid accumulation and lipids metabolism-related genes, which were detected by a TG kit, a TC kit, Oil red O staining and quantitative real-time PCR, respectively. Western blot was used to measure the level of asymmetric dimethyl arginine (ADMA), and PRMTs expression was assessed by qPCR. The underlying mechanism was analyzed using co-immunoprecipitation (co-IP), IP, immunofluorescence staining, bioinformatic analysis and western blot. Results showed that Kae decreased the content of intracellular TG and TC, inhibited cellular lipid accumulation, and reduced the expression of FAS, ACC and SREBP-1c in cell model. Moreover, Kae increased the level of ADMA and PRMT-1, and PRMT-1 knockdown reversed the effect of Kae inhibiting lipid accumulation in cell model. Mechanistically, PRMT-1 overexpression inhibited arginine methylation of SCD1 at arginine (R)175 site. In concluiosn, kae inhibited lipid accumulation in AFLD cell model through PRMT-1-mediated SCD1 arginine methylation. This study may provide a novel therapeutic strategy for AFLD.
{"title":"Kaempferol inhibits lipid accumulation in alcoholic fatty liver disease through PRMT-1-mediated arginine methylation of SCD1","authors":"Jiahui Li, Zheng Zhou, Qiaoling Zhou","doi":"10.1038/s41429-025-00859-y","DOIUrl":"10.1038/s41429-025-00859-y","url":null,"abstract":"Alcoholic fatty liver disease (AFLD) is a type of liver damage caused by excessive alcohol consumption. Kaempferol (Kae) has been shown to have good anti-cancer effects. This study aimed to investigate the effect and the mechanism of Kae on AFLD at the cellular level. THLE-2 cells were treated with ethanol to establish an AFLD cell model. The effect of Kae on lipid accumulation was assessed through the level of intracellular triglyceride (TG), intracellular total cholesterol (TC), cellular lipid accumulation and lipids metabolism-related genes, which were detected by a TG kit, a TC kit, Oil red O staining and quantitative real-time PCR, respectively. Western blot was used to measure the level of asymmetric dimethyl arginine (ADMA), and PRMTs expression was assessed by qPCR. The underlying mechanism was analyzed using co-immunoprecipitation (co-IP), IP, immunofluorescence staining, bioinformatic analysis and western blot. Results showed that Kae decreased the content of intracellular TG and TC, inhibited cellular lipid accumulation, and reduced the expression of FAS, ACC and SREBP-1c in cell model. Moreover, Kae increased the level of ADMA and PRMT-1, and PRMT-1 knockdown reversed the effect of Kae inhibiting lipid accumulation in cell model. Mechanistically, PRMT-1 overexpression inhibited arginine methylation of SCD1 at arginine (R)175 site. In concluiosn, kae inhibited lipid accumulation in AFLD cell model through PRMT-1-mediated SCD1 arginine methylation. This study may provide a novel therapeutic strategy for AFLD.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 11","pages":"686-696"},"PeriodicalIF":2.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-06DOI: 10.1038/s41429-025-00854-3
Kenichi Matsuda
α/β hydrolase fold thioesterases (TEs) play fundamentally important roles in polyketide and non-ribosomal peptide biosynthesis. Type-I TEs, fused at the C-terminus of multi-modular enzymatic assembly lines, dictate the overall molecular shapes of assembly-line products, while standalone type-II TEs maintain assembly-line activity through proofreading functions. Beyond these established roles, recent studies have elucidated several distinct TE functions that expand the functional versatility of these enzymes. This review summarizes recently discovered non-canonical functions of TEs in bacterial non-ribosomal peptide biosynthesis.
{"title":"Non-canonical thioesterases in bacterial non-ribosomal peptide biosynthesis","authors":"Kenichi Matsuda","doi":"10.1038/s41429-025-00854-3","DOIUrl":"10.1038/s41429-025-00854-3","url":null,"abstract":"α/β hydrolase fold thioesterases (TEs) play fundamentally important roles in polyketide and non-ribosomal peptide biosynthesis. Type-I TEs, fused at the C-terminus of multi-modular enzymatic assembly lines, dictate the overall molecular shapes of assembly-line products, while standalone type-II TEs maintain assembly-line activity through proofreading functions. Beyond these established roles, recent studies have elucidated several distinct TE functions that expand the functional versatility of these enzymes. This review summarizes recently discovered non-canonical functions of TEs in bacterial non-ribosomal peptide biosynthesis.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 11","pages":"639-650"},"PeriodicalIF":2.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A novel actinobacterium strain, designated HUAS ZL42T, was isolated from the leaves of Cynara scolymus. Its taxonomic position was characterized using a polyphasic method. Strain HUAS ZL42T produced spiral spore chains consisting of rod-shaped or ovoid spores with smooth surfaces on Gause’s synthetic No.1 medium. The cell wall of strain HUAS ZL42T contained ll-diaminopimelic acid as a diagnostic amino acid. Whole-cell hydrolysates contained galactose and mannose. The predominant cellular fatty acids (>10.0%) of strain HUAS ZL42T were iso-C14:0, anteiso-C15:0 and iso-C16:0. The menaquinones were MK-9 (H6), MK-9 (H4) and MK-9 (H8). The 16S rRNA gene sequence analysis showed that strain HUAS ZL42T exhibited the highest similarities to Streptomyces cyslabdanicus K04-0144T (98.6%), Streptomyces cinnabarigriseus JS360T (98.6%), Streptomyces cyaneus CGMCC 4.1671T (98.4%) and Streptomyces corchorusii DSM 40340T (98.4%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HUAS ZL42T formed an independent subclade. Phylogenetic analysis based on five housekeeping gene sequences demonstrated that strain HUAS ZL42T was most closely related to S. cyaneus CGMCC 4.1671T. However, the ANIm and dDDH between strain HUAS ZL42T and S. cyaneus CGMCC 4.1671T were 87.17% and 28.90%, respectively, far less than 96.7% and 70% cut-off points recommended for delineating Streptomyces species, suggesting that strain HUAS ZL42T was a novel Streptomyces species. On the basis of phenotypic and genotypic differentiation from tested strains, it is proposed that strain HUAS ZL42T represents a novel species of the genus Streptomyces, named Streptomyces secundicynarae sp. nov. The type strain is HUAS ZL42T (=MCCC 1K09444T = JCM 37325T).
{"title":"Streptomyces secundicynarae sp. nov., a novel actinomycete isolated from the leaves of Cynara scolymus","authors":"Yu Song, Ting Tang, Ping Mo, Zhilong Wu, Fengying Liu, Aihua Deng","doi":"10.1038/s41429-025-00853-4","DOIUrl":"10.1038/s41429-025-00853-4","url":null,"abstract":"A novel actinobacterium strain, designated HUAS ZL42T, was isolated from the leaves of Cynara scolymus. Its taxonomic position was characterized using a polyphasic method. Strain HUAS ZL42T produced spiral spore chains consisting of rod-shaped or ovoid spores with smooth surfaces on Gause’s synthetic No.1 medium. The cell wall of strain HUAS ZL42T contained ll-diaminopimelic acid as a diagnostic amino acid. Whole-cell hydrolysates contained galactose and mannose. The predominant cellular fatty acids (>10.0%) of strain HUAS ZL42T were iso-C14:0, anteiso-C15:0 and iso-C16:0. The menaquinones were MK-9 (H6), MK-9 (H4) and MK-9 (H8). The 16S rRNA gene sequence analysis showed that strain HUAS ZL42T exhibited the highest similarities to Streptomyces cyslabdanicus K04-0144T (98.6%), Streptomyces cinnabarigriseus JS360T (98.6%), Streptomyces cyaneus CGMCC 4.1671T (98.4%) and Streptomyces corchorusii DSM 40340T (98.4%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HUAS ZL42T formed an independent subclade. Phylogenetic analysis based on five housekeeping gene sequences demonstrated that strain HUAS ZL42T was most closely related to S. cyaneus CGMCC 4.1671T. However, the ANIm and dDDH between strain HUAS ZL42T and S. cyaneus CGMCC 4.1671T were 87.17% and 28.90%, respectively, far less than 96.7% and 70% cut-off points recommended for delineating Streptomyces species, suggesting that strain HUAS ZL42T was a novel Streptomyces species. On the basis of phenotypic and genotypic differentiation from tested strains, it is proposed that strain HUAS ZL42T represents a novel species of the genus Streptomyces, named Streptomyces secundicynarae sp. nov. The type strain is HUAS ZL42T (=MCCC 1K09444T = JCM 37325T).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"593-599"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-29DOI: 10.1038/s41429-025-00852-5
Shasha Li, Xiaomeng Hao, Yan Li, Maoluo Gan
Emericellopsic acid (1), the first B/C ring-rearranged fusidane-type antibiotic possessing a 6/5/7/5-fused ring framework, together with seven known helvolic acid derivatives, was isolated from the sponge-associated fungus Emericellopsis maritima IMB18-123 cultivated with autoclaved Pseudomonas aeruginosa. The structure of 1 was determined by extensive spectroscopic data analysis combined with ECD calculation. Compound 1 exhibited moderate antimicrobial activities against Staphylococcus aureus and S. epidermidis with the minimum inhibition concentration of 4−8 μg ml−1.
{"title":"Emericellopsic acid, a helvolic acid derivative with a 6/5/7/5 tetracyclic skeleton from sponge-derived Emericellopsis maritima","authors":"Shasha Li, Xiaomeng Hao, Yan Li, Maoluo Gan","doi":"10.1038/s41429-025-00852-5","DOIUrl":"10.1038/s41429-025-00852-5","url":null,"abstract":"Emericellopsic acid (1), the first B/C ring-rearranged fusidane-type antibiotic possessing a 6/5/7/5-fused ring framework, together with seven known helvolic acid derivatives, was isolated from the sponge-associated fungus Emericellopsis maritima IMB18-123 cultivated with autoclaved Pseudomonas aeruginosa. The structure of 1 was determined by extensive spectroscopic data analysis combined with ECD calculation. Compound 1 exhibited moderate antimicrobial activities against Staphylococcus aureus and S. epidermidis with the minimum inhibition concentration of 4−8 μg ml−1.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"580-585"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-25DOI: 10.1038/s41429-025-00851-6
Karin Hamada, Yoshihiro Watanabe, Yuta Kikuchi, Hayama Tsutsumi, Haruki Azami, Hiroki Kojima, Sho Kato, Akihiro Sugawara, Yuki Inahashi, Kenichi Nonaka, Rei Hokari, Aki Ishiyama, Yasuko Araki, Kona Yamashita, Tadashi Takahashi, Kotaro Ito, Yukihiro Asami, Masato Iwatsuki
To discover novel natural compounds by awakening unexplored or silent BGCs in fungi, our research group has explored the cultured broths of the laeA-introduced mutant fungal strains. In this study, we report the isolation of a new benzoyl sesquiterpenoid, aoganolide (4), as well as three known compounds, decarboxyaltenusin (1), altenusin (2), and penipyranicin B (3), from the cultured broth of Talaromyces sp. KTF-0021, which was a laeA-introduced mutant of FKI-5759 strain. The planar structure of 4 was elucidated by spectroscopic analysis and the absolute configuration of 4 was determined by the calculated ECD spectral method. Among them, 4 showed antimalarial activity with IC50 values of 4.37 and 6.46 µg ml−1 against Plasmodium falciparum FCR3 and K1 strains, respectively. The laeA-introduced mutant strain produced 2, 3, and 4 with higher productivity (47, 623, and 38 mg l−1) than the wild-type strain (1.4, 0.8, and 7.7 mg l−1), respectively, suggesting this method is useful to expand the chemical diversity of natural products.
{"title":"New benzoyl sesquiterpenoid, aoganolide, produced by Talaromyces sp. KTF-0021 strain (laeA-introduced mutant of FKI-5759 strain)","authors":"Karin Hamada, Yoshihiro Watanabe, Yuta Kikuchi, Hayama Tsutsumi, Haruki Azami, Hiroki Kojima, Sho Kato, Akihiro Sugawara, Yuki Inahashi, Kenichi Nonaka, Rei Hokari, Aki Ishiyama, Yasuko Araki, Kona Yamashita, Tadashi Takahashi, Kotaro Ito, Yukihiro Asami, Masato Iwatsuki","doi":"10.1038/s41429-025-00851-6","DOIUrl":"10.1038/s41429-025-00851-6","url":null,"abstract":"To discover novel natural compounds by awakening unexplored or silent BGCs in fungi, our research group has explored the cultured broths of the laeA-introduced mutant fungal strains. In this study, we report the isolation of a new benzoyl sesquiterpenoid, aoganolide (4), as well as three known compounds, decarboxyaltenusin (1), altenusin (2), and penipyranicin B (3), from the cultured broth of Talaromyces sp. KTF-0021, which was a laeA-introduced mutant of FKI-5759 strain. The planar structure of 4 was elucidated by spectroscopic analysis and the absolute configuration of 4 was determined by the calculated ECD spectral method. Among them, 4 showed antimalarial activity with IC50 values of 4.37 and 6.46 µg ml−1 against Plasmodium falciparum FCR3 and K1 strains, respectively. The laeA-introduced mutant strain produced 2, 3, and 4 with higher productivity (47, 623, and 38 mg l−1) than the wild-type strain (1.4, 0.8, and 7.7 mg l−1), respectively, suggesting this method is useful to expand the chemical diversity of natural products.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"586-592"},"PeriodicalIF":2.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-24DOI: 10.1038/s41429-025-00847-2
Anum Munir, Alan Janbey, Bilawal Sajjad, Kowsalya V. Perumal, Hajra Qayyum, Marriam Bakhtiar
The human skin microbiota, comprising a diverse range of microorganisms, including bacteria, viruses, and fungi, plays an important role in maintaining skin health and protecting against pathogenic invasions. Among these microorganisms, certain bacteria produce bacteriocins, which are ribosomal peptides with potent antimicrobial properties. This study presents a novel computational approach to identify and predict bacteriocins from microbial genomes comprising sebaceous region of the skin, aiming to explore their therapeutic potential. Through genome analysis using advanced bioinformatics tools, we identified potential genes, operons, open reading frames (ORFs), and promoter regions linked to bacteriocin production. The BAGEL4 platform was employed to detect structural bacteriocin genes, while modelling bacterial growth and bacteriocin expression under various environmental conditions was conducted using MATLAB’s SimBiology application. The results revealed the optimal conditions for bacteriocin production and highlighted promising candidates for further experimental validation. These findings underscore the significance of skin microbiota as a source of novel bacteriocins, offering potential alternatives to traditional antibiotics amidst rising antimicrobial resistance.
{"title":"Bioinformatics-driven discovery of skin microbiota bacteriocins as potential antibiotics and probiotics","authors":"Anum Munir, Alan Janbey, Bilawal Sajjad, Kowsalya V. Perumal, Hajra Qayyum, Marriam Bakhtiar","doi":"10.1038/s41429-025-00847-2","DOIUrl":"10.1038/s41429-025-00847-2","url":null,"abstract":"The human skin microbiota, comprising a diverse range of microorganisms, including bacteria, viruses, and fungi, plays an important role in maintaining skin health and protecting against pathogenic invasions. Among these microorganisms, certain bacteria produce bacteriocins, which are ribosomal peptides with potent antimicrobial properties. This study presents a novel computational approach to identify and predict bacteriocins from microbial genomes comprising sebaceous region of the skin, aiming to explore their therapeutic potential. Through genome analysis using advanced bioinformatics tools, we identified potential genes, operons, open reading frames (ORFs), and promoter regions linked to bacteriocin production. The BAGEL4 platform was employed to detect structural bacteriocin genes, while modelling bacterial growth and bacteriocin expression under various environmental conditions was conducted using MATLAB’s SimBiology application. The results revealed the optimal conditions for bacteriocin production and highlighted promising candidates for further experimental validation. These findings underscore the significance of skin microbiota as a source of novel bacteriocins, offering potential alternatives to traditional antibiotics amidst rising antimicrobial resistance.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"606-620"},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deep-sea-derived microorganisms are quite attractive as resources for new secondary metabolites, enzymes, and gene discovery. We have isolated many marine microorganisms from deep-sea creatures and screened the new secondary metabolites produced by them. Two new molecules designated amino-naphthoic acid derivatives (1 and 2) were obtained by biological transformation using the deep-sea derived bacterium Serinicoccus marinus KDM482 successfully. Structural analysis using 1D and 2D NMR and MS data revealed that both 1 and 2 were dimerized compounds of 3-amino-2-naphthoic acid. In biological assays, 1 and 2 moderately inhibited the growth of Malme-3M cells.
{"title":"New amino-naphthoic acid derivatives produced by biological transformation using the deep-sea-derived bacterium Serinicoccus marinus KDM482","authors":"Mai Sakaguchi, Katsuki Kikuchi, Ryota Okamura, Akito Taniguchi, Kenichiro Nagai, Reiko Seki, Masashi Ando, Teruyoshi Tanaka, Takashi Fukuda","doi":"10.1038/s41429-025-00845-4","DOIUrl":"10.1038/s41429-025-00845-4","url":null,"abstract":"Deep-sea-derived microorganisms are quite attractive as resources for new secondary metabolites, enzymes, and gene discovery. We have isolated many marine microorganisms from deep-sea creatures and screened the new secondary metabolites produced by them. Two new molecules designated amino-naphthoic acid derivatives (1 and 2) were obtained by biological transformation using the deep-sea derived bacterium Serinicoccus marinus KDM482 successfully. Structural analysis using 1D and 2D NMR and MS data revealed that both 1 and 2 were dimerized compounds of 3-amino-2-naphthoic acid. In biological assays, 1 and 2 moderately inhibited the growth of Malme-3M cells.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"573-576"},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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