Journal of Antibiotics最新文献

A novel actinobacterial strain NEAU-NA10^T showing antifungal activity and plant growth-promoting ability was isolated from the rhizosphere soil of strawberry seedlings collected from Ya'an City, Sichuan Province, China (28°51' N, 101°56' E). A polyphasic taxonomic study was used to establish the status of strain NEAU-NA10^T. 16S rRNA gene sequence analysis revealed that strain NEAU-NA10^T belongs to the genus Streptomyces and shares the highest similarity (99.31%) with Streptomyces canarius CGMCC 4.1581^T. Whole-genome comparisons with its reference strains demonstrated that the average nucleotide identity (ANIm) and digital DNA-DNA hybridization (dDDH) values ranged from 86.74 to 87.75% and 27.0 to 30.1%, respectively. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol. The diagnostic sugars in cell hydrolysates were determined to be ribose, and the cell wall contained _LL-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were MK-9(H₄), MK-9(H₆) and MK-9(H₈). The predominant cellular fatty acids (>10%) were C_16:0, C_17:0, C_18:0, and anteiso-C_18:0. Meanwhile, genomic analysis revealed a genome size of 9,459,621 bp and a DNA G + C content of 71.81%, and indicated that strain NEAU-NA10^T has the potential to degrade cellulose and produce amylase. Based on phenotypic, chemotaxonomic, and genotypic studies, strain NEAU-NA10^T is considered to be a novel species of the genus Streptomyces, for which the name Streptomyces aurantiaciflavus sp. nov. is proposed, with NEAU-NA10^T (=MCCC 1K08700^T = JCM 36416^T) as the type strain.

Two new α-pyrone compounds designated marinapyrones A (1) and B (2) were isolated along with the known related compound micropyrone B (3) from the culture broth of rhizosphere-derived actinomycete strain W21-0103. The structures of 1 and 2 were elucidated by spectroscopic data analyses, including 1D and 2D NMR. Compounds 1-3 exhibited weak antioxidant activity in a radical scavenging assay.

Typhoidal Salmonella continues to pose a severe public health threat, with its management increasingly complicated by the rise of antimicrobial resistance. This study investigated 50 clinical isolates of Salmonella Typhi (S. Typhi) and S. Paratyphi to delineate the association between antibiotic resistance, biofilm formation, and nanoscale mechanical traits. Our results revealed that 22% of isolates were multidrug-resistant (MDR), displaying the classical resistance pattern against ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Among these resistant isolates, 54% formed biofilms, and this trait was strongly associated with multidrug resistance; 100% of MDR isolates were biofilm-positive (p = 0.001). Atomic force microscopy (AFM) revealed a distinct "hard-shell" bio-mechanical phenotype in biofilm-positive isolates, exhibiting significantly higher stiffness (31.3 ± 9.8 vs. 8.2 ± 2.3 kPa), adhesion force (17.8 ± 4.6 vs. 5.4 ± 1.4 nN), and surface roughness (11.6 ± 3.2 vs. 3.6 ± 1.0 nm) (p < 0.001 for all). This mechanical reinforcement was accompanied by a 2.7-fold increase in cell surface hydrophobicity (80.4 ± 8.9% vs. 30.3 ± 11.9%) and a 13.5-fold enhancement in desiccation survival (40.4 ± 10.7% vs. 3.0 ± 2.9%). Correlation analysis revealed these traits are highly interdependent (ρ = 0.78--0.89, p < 0.001), forming a cohesive "hard-shell" persistence phenotype. In summary, multidrug-resistant Salmonella possesses a unified trait that enhances its structural strength, ability to adhere, and environmental survival.

Thioester reductase domain in nonribosomal peptide synthetases catalyzes reductive offloading to produce aldehyde- or alcohol-containing peptides. By genome mining focusing on thioester reductase domains, we isolated aquimarinols A-D, four novel polyketide-peptide hybrid metabolites isolated from the sponge-derived strain Aquimarina muelleri LMG 22569. Structural elucidation of aquimarinols revealed a β-formamidated fatty acid (FA) moiety and a threoninol unit linked by a peptide bond or an ester bond. The biosynthesis of aquimarinols is proposed to proceed via a hybrid trans-AT polyketide synthase-nonribosomal peptide synthetase pathway coupled with modification enzymes.

Aminoacyl-tRNAs, charged by aminoacyl-tRNA synthetases with cognate amino acids, are essential for protein synthesis in primary metabolism. Beyond this canonical role, increasing evidence highlights their involvement in natural product biosynthesis. In this review, we first describe the biosynthesis of the aminoacyl nucleoside sulfamate ascamycin from Streptomyces sp. 80H647, highlighting the discovery of the alanyl-tRNA synthetase-like enzyme AcmF through an AI-driven "Forecasting Biosynthesis" approach. Leveraging recent advances in AlphaFold 3, we constructed complex models of a broadened repertoire of aminoacyl-tRNA-dependent enzymes to provide preliminary structure-function insights. These include the isoleucyl-tRNA synthetase-like enzyme SbzA, Gcn5-related N-acetyltransferase-fold transferases, cyclodipeptide synthase family enzymes, and lantibiotic dehydratase-like peptide aminoacyl-tRNA ligases. The catalytic mechanisms of these aminoacyl-tRNA-dependent enzymes are summarized in detail in this review.

Fungi have a potential to produce a variety of natural products for their survival by utilizing dozens of biosynthetic gene clusters (BGCs). Fungal BGCs are typically conserved in species but recent studies showed that many BGCs are maintained in limited number of strains. However, little is reported for the products of strain specific BGCs. In this study, we analyzed publicly available genomic data of human pathogenic fungus Aspergillus lentulus and identified seven strain-specific BGCs in addition to (-)- and (+)-auranthine BGCs. One of these BGCs, leq cluster, was found in nine of thirteen A. lentulus strains and a new compound named lentoquinazoline (1) appeared in the metabolites when non-ribosomal peptide synthetase (NRPS) gene leqA was heterologously expressed in Aspergillus nidulans. The structure of 1 was determined by the combination of 2D NMR analysis and advanced Marfey's method to be composed of anthranilic acid, L-leucine and L-asparagine. Whereas 6-6-6 tricyclic quinazoline-synthesizing NRPSs typically contain an epimerase domain and incorporate one molecule of D-amino acid to the product, LeqA was found to introduce only L-amino acids due to the mutations in the active site of the epimerase domain.

Genome mining is a powerful strategy for finding biosynthetic gene clusters (BGCs) for unprecedented natural products and their biosynthetic mechanisms. In this study, to obtain novel type polyketides, we performed genome mining focusing on three perspectives for novelty: 1) amino acid sequence-based classification, 2) unique domain architectures of polyketide synthase, and 3) predicted structural features from protein modeling. As a result, we discovered a BGC consisting of a highly reducing polyketide synthase and a non-reducing polyketide synthase (NR-PKS), which harbors noncanonical tandem acyl carrier protein (ACP) domains and a structurally characteristic thioesterase (TE) domain. Heterologous expression revealed that the cyrl cluster produces a novel dimer of long-chain alkylresorcinolic acid (1). Furthermore, site-directed mutagenesis of each ACP domain revealed that both domains are essential for efficient dimerization. This study provides the first example of a fungal dimer-forming NR-PKS in which the tandem ACP domains work "in-series" with nonredundant roles to construct a dimeric long-chain alkylresorcinolic acid. The in silico analysis suggested that the TE domain led the substrate to a dimerizable form. Since 1 is structurally related to integracins with HIV-1 integrase inhibition, our findings provide insight into integracins biosynthesis and offer a basis for generating new integracin derivatives.