Search Results (101)

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder with a pressing need for novel therapeutics. However, current medications only offer symptomatic relief, without tackling the underlying pathology. To explore the bioactive potential of marine-derived fungi, this study focused on Aspergillus terreus C23-3, a strain isolated from the coral Pavona cactus in Xuwen County, China, which showed a richer metabolite fingerprint among the three deposited A. terreus strains. AntiSMASH analysis based on complete genome sequencing predicted 68 biosynthetic gene clusters (BGCs) with 7 BGCs synthesizing compounds reported to have anti-AD potential, including benzodiazepines, benzaldehydes, butenolides, and lovastatin. Liquid chromatography coupled with mass spectrometry (LC-MS)-based combinational metabolomic annotation verified most of the compounds predicted by BGCs with the acetylcholinesterase (AChE) inhibitor territrem B characterized from its fermentation extract. Subsequently, molecular docking showed that these compounds, especially aspulvione B1, possessed strong interactions with AD-related targets including AChE, cyclin-dependent kinase 5-p25 complex (CDK5/p25), glycogen synthase kinase-3β (GSK-3β), and monoamine oxidase-B (MAO-B). In conclusion, the genomic–metabolomic analyses and molecular docking indicated that C23-3 is a high-value source strain for anti-AD natural compounds. Full article

Xenorhabdus species are entomopathogenic bacteria that live in symbiosis with Steinernema nematodes and produce a wide range of bioactive secondary metabolites. This study aimed to characterize the complete genomes and biosynthetic potential of two novel Xenorhabdus isolates, ALN7.1 and ALN11.5, recovered from Steinernema lamjungense collected in Northern Thailand. High-quality genome assemblies were generated, and phylogenomic comparisons confirmed that both isolates belonged to the recently described species Xenorhabdus thailandensis. The assembled genomes were approximately 4.02 Mb in size, each comprising a single circular chromosome with a GC content of 44.6% and encoding ~3800 protein-coding sequences, consistent with the features observed in other members of the genus. Biosynthetic gene cluster (BGCs) prediction using antiSMASH identified 19 BGCs in ALN7.1 and 18 in ALN11.5, including known clusters for holomycin, pyrrolizixenamide, hydrogen cyanide, and gamexpeptide C, along with several uncharacterized clusters, suggesting unexplored metabolic potential. Comparative analyses highlighted conserved yet strain-specific BGC profiles, indicating possible diversification within the species. These results provide genomic insights into X. thailandensis ALN7.1 and ALN11.5 and support their potential as valuable sources for the discovery of novel natural products and for future biotechnological applications. Full article

Background: Endophytic fungi are prolific sources of bioactive metabolites with potential in pharmaceutical and biotechnological applications. Methods: Here, the endophytic fungus, Alternaria alstroemeriae S6, was isolated from Veronica acinifolia (speedwell), and conducted its anti-microbial activities, whole-genome sequencing and metabolome analysis. Results: The ethyl acetate extract of this fungus exhibited strong anti-bacterial activity and the inhibition zones, induced by the fungal extract at 20 mg/mL, reached 16.25 ± 0.5 mm and 26.5 ± 0.5 mm against Gram-positive and Gram-negative bacteria. To unravel the biosynthetic potential for anti-bacterial compounds, whole-genome sequencing was conducted on A. alstroemeriae S6, resulting in a high-quality assembly of 42.93 Mb encoding 13,885 protein-coding genes. Comprehensive functional genome annotation analyses, including gene ontology (GO) terms, clusters of orthologous groups (COGs), Kyoto encyclopedia of genes and genomes (KEGG), carbohydrate-active enzymes (CAZymes), and antibiotics and secondary metabolites analysis shell (antiSMASH) analyses, were performed. According to the antiSMASH analysis, 58 biosynthetic gene clusters (BGCs), including 16 non-ribosomal peptide synthetases (NRPSs), 21 terpene synthases, 12 polyketide synthetases (PKSs), and 9 hybrids, were identified. In addition, succinic acid was identified as the major metabolite within the fungal extract, while 20 minor bioactive compounds were identified through LC-MS/MS-based molecular networking on a GNPS database. Conclusions: These findings support the biotechnological potential of A. alstroemeriae S6 as an alternative producer of succinic acid, as well as novel anti-bacterial agents. Full article

A novel actinobacterial strain, designated E54^T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54^T within the genus Lentzea, showing highest similarity to Lentzea waywayandensis DSM 44232^T (98.9%) and Lentzea flava NBRC 15743^T (98.5%). However, whole-genome comparisons revealed that the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between E54^T and these related strains were below the thresholds for species delineation. Strain E54^T exhibited typical morphological characteristics of the genus Lentzea, forming a branched substrate. It grew optimally at 28–30 °C, pH 7.0–9.0, and tolerated up to 10% NaCl. The cell wall contained meso-diaminopimelic acid, the predominant menaquinone was MK-9(H₄), and major fatty acids included iso-C_16:0. The polar lipid profile comprised diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, hydroxyphosphatidyl ethanolamine, and an unidentified lipid. The characteristic amino acid type of the cell wall was meso-DAP. Whole-cell hydrolysis experiments revealed the characteristic cell wall sugar fractions: ribose and galactose. The genome of strain E54^T is approximately 8.0 Mb with a DNA G+C content of 69.38 mol%. Genome mining revealed 39 biosynthetic gene clusters (BGCs), including non-ribosomal peptide synthetases (NRPS), polyketide synthases (PKS), terpenes, and siderophores. Comparative antiSMASH-based genome analysis across 38 Lentzea strains further demonstrated the genus’ remarkable biosynthetic diversity. NRPS and type I PKS (T1PKS) were the most prevalent BGC types, indicating a capacity to synthesize structurally complex and pharmacologically relevant metabolites. Together, these findings underscore the untapped biosynthetic potential of the genus Lentzea and support the proposal of strain E54^T as a novel species. The strain E54^T (=JCM 34936^T = GDMCC 4.216^T) should represent a novel species, for which the name Lentzea xerophila sp. nov. is proposed. Full article

Staphylococcus pseudintermedius, an opportunistic pathogen of veterinary and zoonotic concern, harbors diverse biosynthetic gene clusters (BGCs) that may contribute to its ecological fitness and virulence. In this study, we performed a comparative genomic analysis of 6815 S. pseudintermedius isolates. Using Roary, we identified core and accessory genomes, revealing the subtilosin A gene (sboA) as part of the accessory genome, present in a subset of S. pseudintermedius isolates from clinical (n = 657), environmental (n = 1031), and unclassified sources (n = 487). AntiSMASH v8.0.0 analysis confirmed the presence of subtilosin A BGCs annotated as a sactipeptide with low similarity confidence to Bacillus subtilis subsp. spizizenii ATCC 6633 subtilosin A cluster. Further characterization using BAGEL4 identified multiple genes homologous to the Bacillus subtilis subtilosin A biosynthetic machinery (sbo-albABCDEFG), although albB, albG, and sboX were not annotated, raising questions about cluster completeness and functionality. BLAST v2.12.0 analysis of the full BGC identified by BAGEL4, revealing high conservation (99.6–100% pairwise identity) of gene content and order in 395 clinical, 593 environmental, and 417 unclassified S. pseudintermedius isolates. Incomplete clusters were identified in 763 clinical, 942 environmental, and 201 unclassified S. pseudintermedius isolates. The discrepancy between the number of isolates containing sboA and those harboring the full cluster may reflect evolutionary divergence or could be attributed to limitations in assembly quality. The functional implications of the identified cluster in S. pseudintermedius remain to be elucidated; however, its potential role in conferring competitive fitness by inhibiting closely related species is supported by previous findings in other staphylococci. Full article

Pear black spot disease seriously threatens the pear industry. Currently, its control mainly relies on chemical fungicides while biological control using antagonistic microorganisms represents a promising alternative approach. This study identified and characterized Bacillus velezensis TRMB57782 as a biocontrol strain through whole-genome sequencing. AntiSMASH analysis predicted the strain’s potential to produce secondary metabolites such as surfactin, difficidin, and bacilysin. In vitro experiments demonstrated that TRMB57782 inhibited the growth of Alternaria gaisen. In vivo experiments using excised branches and pear fruits at two different stages also showed significant control effects. A preliminary exploration of the metabolic substances of TRMB57782 was carried out. The strain can produce siderophores and three biocontrol enzymes. Crude extracts obtained by the hydrochloric acid precipitation and ammonium sulfate saturation precipitation of the bacterial liquid exhibited significant activity and volatile organic compounds showed biocontrol activity. Meanwhile, the effects of strain TRMB57782 on the hyphae of pathogenic fungi were studied, leading to hyphal atrophy and spore shrinkage. This paper provides an effective biocontrol strategy for fragrant pear black spot disease, reveals the antibacterial mechanism of Bacillus velezensis TRMB57782, and offers a new option for the green control of pear black spot disease. Full article

Over the past decade, microbial natural products research has witnessed a transformative “deep-mining era” driven by key technological advances such as high-throughput sequencing (e.g., PacBio HiFi), ultra-sensitive HRMS (resolution ≥ 100,000), and multi-omics synergy. These innovations have shifted discovery from serendipitous isolation to data-driven, targeted mining. These innovations have transitioned discovery from serendipitous isolation to data-driven targeted mining. Genome mining pipelines (e.g., antiSMASH 7.0 and DeepBGC) can now systematically discover hidden biosynthetic gene clusters (BGCs), especially in under-explored taxa. Metabolomics has achieved unprecedented accuracy, enabling researchers to target novel compounds in complex extracts. Integrated strategies—combining genomic prediction, metabolomics analysis, and experimental validation—constitute new paradigms of current “deep mining”. This review provides a systematic overview of 185 novel microbial natural products discovered between 2018 and 2024, and dissects how these technological leaps have reshaped the discovery paradigm from traditional isolation to data-driven mining. Full article

This study explored the biosynthetic mechanisms and structural diversity of pyoverdines (PVDs) produced by Pseudomonas fulva. Genomic analysis using antiSMASH identified the PVD biosynthetic gene cluster, although the C-terminal peptide sequence could not be predicted. Subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed the full peptide structure, including modified residues, such as N-acetylhydroxyornithine and cyclohydroxyornithine, and confirmed the presence of several PVD isoforms with different chromophore side chains. Comparative LC-MS analysis across Pseudomonas species demonstrated that P. fulva produces unique PVD molecular mass patterns. The bioinformatic and structural modeling of non-ribosomal peptide synthetase PvdL open reading frame 3 revealed that the A2 and A3 adenylation domains are lysine selective. Although their sequences differ from known lysine-specific signatures, AlphaFold3-based structural prediction revealed conserved substrate-binding configurations, suggesting that similar substrate-binding features may have arisen independently. Notably, Thr²⁹⁷, a unique residue in the non-ribosomal code, likely plays a key role in lysine recognition. The high degree of sequence similarity between the A2 and A3 domains may reflect domain duplication and could be involved in the diversification of the PVD structure. Further functional and ecological studies are required to assess the physiological significance of P. fulva PVDs in microbial iron acquisition. Full article

This study aims to elucidate the genomic characteristics of Bacillus subtilis MGE 2012, a strain isolated from Korean traditional fermented food, meju, which contributes to its high enzyme activity and potential applications. The whole genome sequence of B. subtilis MGE 2012 was assembled using MEGAHIT, annotated using RAST and BLASTKOALA v3.1. Phylogenetic analysis placed MGE 2012 within the Bacillus clade, showing high similarity to B. subtilis NCIB 3610 and B. subtilis ATCC 6051. AntiSMASH analysis identified 14 biosynthetic gene clusters (BGCs) capable of producing various secondary metabolites, including subtilosin, bacillibactin, fengycin, bacilysin, plipastatin, and surfactin. This study provides an overview of the whole genome and secondary metabolite profile of B. subtilis MGE 2012, emphasizing its potential applications in biotechnology. While the primary focus of this study was to explore the genomic characteristics and secondary metabolite profile, future research could delve deeper into genome mining for enzyme activities and their applications. Full article

Soil, rhizosphere, and plant-associated microorganisms can enhance plant growth and health. A genomic analysis of these microbes revealed the key characteristics contributing to their beneficial effects. Following a field survey in Panama, four bacterial isolates with plant growth-promoting traits (PGPT) in rice (Oryza sativa L.) were identified. In this study, we sequenced, assembled, and annotated the genomes of Lysinibacillus fusiformis C6 and 24, and Bacillus cereus D23 and 59. The C6 genome was 4,754,472 bp long with 10 contigs, 37.62% guanine-cytosine (GC) content, and 4657 coding sequences (CDS). The 24 genome was 4,683,219 bp with five contigs, 37.65% GC content, and 4550 CDS. The D23 genome was 6,199,908 bp long with 18 contigs, 34.84% GC content, and 6141 CDS. The 59 genome was 6,194,462 bp with 21 contigs, 34.87% GC content, and 6122 CDS. Digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) confirmed that C6 and 24 belong to Lysinibacillus fusiformis, whereas D23 and 59 belong to the Bacillus cereus species. Further results revealed that these bacteria contained genes characteristic of plant growth-promoting bacteria, such as siderophore, phytohormone auxin (IAA) production, and nitrogen-fixing abilities that promote plant growth. Moreover, the antiSMASH database identified gene clusters involved in secondary metabolite production (biosynthetic gene clusters), such as betalactone, NRPS-like, NRP-siderophore, terpene, and RiPP-like clusters. Moreover, diverse and novel biosynthetic clusters (BCGs) have included non-ribosomal peptides (NRPs), polyketides (PKs), bacteriocins, and ribosomally synthesized and post-transcriptionally modified peptides (RiPPs). This work offers new insights into the genomic basis of the studied strains’ plant growth-promoting capabilities. Full article

Lactiplantibacillus plantarum GUANKE (L. plantarum GUANKE) is a Gram-positive bacterium isolated from the feces of healthy volunteers. Whole-genome sequencing analysis (WGS) revealed that the genome of L. plantarum GUANKE consists of one chromosome and two plasmids, with the chromosome harbors 2955 CDS, 66 tRNAs, and 5 rRNAs. The genome is devoid of virulence factors and Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems. It contains three intact prophage regions and bacteriocin biosynthesis genes (plantaricins K, F, and E), as well as seventeen genomic islands lacking antibiotic resistance or pathogenicity determinants. Functional prediction outcomes identified that the genome of L. plantarum GUANKE is closely related to transcription, carbohydrate transport and metabolism, and amino acid transport and metabolism. Carbohydrate-active enzymes (CAZymes) analysis and GutSMASH analysis revealed that the genome of L. plantarum GUANKE contained 100 carbohydrate-active enzyme genes and two specialized metabolic gene clusters. Safety assessments confirmed that L. plantarum GUANKE neither exhibited β-hemolytic activity nor harbored detectable transferable drug resistance genes. The strain exhibited remarkable acid tolerance and bile salt resistance. Cellular adhesion assays demonstrated moderate binding capacity to Caco-2 intestinal epithelium (4.3 ± 0.007)%. In vitro analyses using lipopolysaccharide (LPS)-stimulated macrophage models demonstrated that L. plantarum GUANKE significantly suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), exhibiting dose-dependent anti-inflammatory activity. In vivo experiments showed that L. plantarum GUANKE was involved in the regulation of the apical junction pathway and interferon pathway in colon tissue of normal mice. Full article

Antarctic microorganisms have genomic characteristics and biological functions to ensure survival in complex habitats, potentially representing bioactive compounds of biotechnological interest. Pseudarthrobacter sp. So.54 is an Antarctic bacteria strain isolated from the rhizospheric soil of Colobanthus quitensis. Our work aimed to study its genomic characteristics and metabolic potential, linked to environmental adaptation and the production of secondary metabolites with possible biotechnological applications. Whole-genome sequencing, assembly, phylogenetic analysis, functional annotation, and genomic islands prediction were performed to determine the taxonomic affiliation and differential characteristics of the strain So.54. Additionally, Biosynthetic Gene Clusters (BGCs) responsible for secondary metabolites production were identified. The assembled genome of strain So.54 has 3,871,805 bp with 66.0% G + C content. Phylogenetic analysis confirmed that strain So.54 belongs to the Pseudarthrobacter genus; nevertheless, its nucleotide and amino acid identity values were below the species threshold. The main metabolic pathways and 64 genomic islands associated with stress defense and environmental adaptation, such as heavy metal resistance genes, were identified. AntiSMASH analysis predicted six BGCs with low or no similarity to known clusters, suggesting potential as novel natural products. These findings indicate that strain So.54 could be a novel Pseudarthrobacter species with significant environmental adaptation and biotechnological potential. Full article

The growing threat of antimicrobial resistance underscores the urgent need to identify new bioactive compounds. In this study, a Streptomyces strain, ACT158, was isolated from a Ramsar wetland ecosystem and found to exhibit broad-spectrum effects against Gram-positive and Gram-negative bacteria, as well as fungal pathogens. The active strain was characterized as S. cavourensis according to its morphology, phylogenetic analysis, average nucleotide identity (ANI), and digital DNA–DNA hybridization (dDDH). Whole-genome sequencing (WGS) and annotation revealed a genome size of 6.86 Mb with 5122 coding sequences linked to carbohydrate metabolism, secondary metabolite biosynthesis, and stress responses. Genome mining through antiSMASH revealed 32 biosynthetic gene clusters (BGCs), including those encoding polyketides, nonribosomal peptides, and terpenes, many of which showed low similarity to known clusters. Comparative genomic analysis, showing high genomic synteny with closely related strains. Unique genomic features of ACT158 included additional BGCs and distinct genes associated with biosynthesis pathways and stress adaptation. These findings highlight the strain’s potential as a rich source of bioactive compounds and provide insights into its genomic basis for antimicrobial production and its ecological and biotechnological significance. Full article

Circular bacteriocins are potent antimicrobials against pathogenic Gram-positives. In searching for marine bacteriocins, an antibacterial peptide (flexusin A) was purified from the fermentation broth of marine bacterium Bacillus flexus R29-2. Genome sequencing and gene annotation revealed the chromosome contained an unknown circular bacteriocin gene cluster. Approaches including shot-gun proteomics analysis, AntiSMASH and BAGEL4 predication as well as the comprehensive sequence alignment, were then conducted, respectively, to verify the correlation of flexusin A with the gene-encoded precursor peptide. The results confirmed that flexusin A was the mature circular bacteriocin of the predicated precursor peptide with six amino acids as leader peptide. Flexusin A was 6098.4 Da in size, with a net charge of +3 and PI of 9.60. It shared the typical saposin-like fold spatial conformation features as commonly found in other circular bacteriocins. Flexusin A was pH, thermal, and protease tolerant. It exhibited a narrow antimicrobial spectrum against Gram-positives, and it can strongly inhibit Staphylococcus aureus by causing cell destruction via membrane destabilization. Taken together, a novel circular bacteriocin flexusin A was identified in this work. The characterization of flexusin A has extended circular bacteriocins family to 26 members. This is also the first report on bacteriocin production by B. flexus. Full article

Penicillium griseofulvum CF3 is a fungus isolated from healthy strawberry soil, with the potential to promote the growth of plants and enhance their resistance to diseases. However, the genome sequence of P. griseofulvum CF3 remains unclear. Therefore, we performed the whole-genome CCS sequencing of P. griseofulvum CF3 using the PacBio Sequel II platform. The assembled genome comprised 104 contigs, with a total length of 37,564,657 bp, encoding 13,252 protein-coding genes. Comprehensive functional annotation was performed using various BLAST databases, including the non-redundant (Nr) protein sequence database, Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), EuKaryotic Orthologous Groups (KOG), and the Carbohydrate-Active enZymes (CAZy) database, to identify and predict protein-coding genes, tRNAs, and rRNAs. The Antibiotics and Secondary Metabolites Analysis Shell (Antismash) analysis identified 50 biosynthetic gene clusters involved in secondary metabolite production within the P. griseofulvum CF3 genome. The whole-genome sequencing of P. griseofulvum CF3 helps us to understand its potential mechanisms in promoting plant growth and enhancing disease resistance, paving the way for the application of the CF3 strain in sustainable crop production. Full article