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Keywords = biosynthetic cluster genes (BGCs)

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29 pages, 6672 KiB  
Article
Discovery of a Novel Antimicrobial Peptide from Paenibacillus sp. Na14 with Potent Activity Against Gram-Negative Bacteria and Genomic Insights into Its Biosynthetic Pathway
by Nuttapon Songnaka, Adisorn Ratanaphan, Namfa Sermkaew, Somchai Sawatdee, Sucheewin Krobthong, Chanat Aonbangkhen, Yodying Yingchutrakul and Apichart Atipairin
Antibiotics 2025, 14(8), 805; https://doi.org/10.3390/antibiotics14080805 - 6 Aug 2025
Abstract
Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial activity of an AMP from a soil-derived bacterial isolate against Gram-negative bacteria. Method: Soil bacteria were isolated and screened for antimicrobial activity. The bioactive peptide was purified and determined its structure and antimicrobial efficacy. Genomic analysis was conducted to predict the biosynthetic gene clusters (BGCs) responsible for AMP production. Results: Genomic analysis identified the isolate as Paenibacillus sp. Na14, which exhibited low genomic similarity (61.0%) to other known Paenibacillus species, suggesting it may represent a novel species. The AMP from the Na14 strain exhibited heat stability up to 90 °C for 3 h and retained its activity across a broad pH range from 3 to 11. Structural analysis revealed that the Na14 peptide consisted of 14 amino acid residues, adopting an α-helical structure. This peptide exhibited bactericidal activity at concentrations of 2–4 µg/mL within 6–12 h, and its killing rate was concentration-dependent. The peptide was found to disrupt the bacterial membranes. The Na14 peptide shared 64.29% sequence similarity with brevibacillin 2V, an AMP from Brevibacillus sp., which also belongs to the Paenibacillaceae family. Genomic annotation identified BGCs associated with secondary metabolism, with a particular focus on non-ribosomal peptide synthetase (NRPS) gene clusters. Structural modeling of the predicted NRPS enzymes showed high similarity to known NRPS modules in Brevibacillus species. These genomic findings provide evidence supporting the similarity between the Na14 peptide and brevibacillin 2V. Conclusions: This study highlights the discovery of a novel AMP with potent activity against Gram-negative pathogens and provides new insight into conserved AMP biosynthetic enzymes within the Paenibacillaceae family. Full article
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18 pages, 8458 KiB  
Article
Exploring the Biosynthetic Potential of Microorganisms from the South China Sea Cold Seep Using Culture-Dependent and Culture-Independent Approaches
by Gang-Ao Hu, Huai-Ying Sun, Qun-Jian Yin, He Wang, Shi-Yi Liu, Bin-Gui Wang, Hong Wang, Xin Li and Bin Wei
Mar. Drugs 2025, 23(8), 313; https://doi.org/10.3390/md23080313 - 30 Jul 2025
Viewed by 268
Abstract
Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, [...] Read more.
Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, to investigate microbial communities and their potential for secondary metabolite production in the South China Sea cold seep. The results indicate microbial composition varied little between two non-reductive sediments but differed significantly from the reductive sediment, primarily due to Planctomycetes and Actinobacteria. Predicting the Secondary Metabolism Potential using Amplicon (PSMPA) predictions revealed 115 strains encoding more than 10 biosynthetic gene clusters (BGCs), with lower BGC abundance in reductive sediment. Culture-dependent studies showed Firmicutes as the dominant cultivable phylum, with strains from shallow samples encoding fewer BGCs. Metagenomic data confirmed distinct microbial compositions and BGC distributions across sediment types, with cold seep type having a stronger influence than geographic location. Certain BGCs showed strong correlations with sediment depth, reflecting microbial adaptation to nutrient-limited environments. This study provides a comprehensive analysis of the metabolic capabilities of South China Sea cold seep microorganisms and reveals key factors influencing their secondary metabolic potential, offering valuable insights for the efficient exploration of cold seep biological resources. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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22 pages, 11051 KiB  
Article
Exploring the Anti-Alzheimer’s Disease Potential of Aspergillus terreus C23-3 Through Genomic Insights, Metabolomic Analysis, and Molecular Docking
by Zeyuan Ma, Longjian Zhou, Zhiyou Yang, Yayue Liu and Yi Zhang
J. Fungi 2025, 11(8), 546; https://doi.org/10.3390/jof11080546 - 23 Jul 2025
Viewed by 448
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Fungal Metabolomics and Genomics)
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18 pages, 1947 KiB  
Article
Whole-Genome Sequencing and Biosynthetic Gene Cluster Analysis of Novel Entomopathogenic Bacteria Xenorhabdus thailandensis ALN 7.1 and ALN 11.5
by Wipanee Meesil, Jiranun Ardpairin, Liam K. R. Sharkey, Sacha J. Pidot, Apichat Vitta and Aunchalee Thanwisai
Biology 2025, 14(8), 905; https://doi.org/10.3390/biology14080905 - 22 Jul 2025
Viewed by 753
Abstract
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 [...] Read more.
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
(This article belongs to the Section Microbiology)
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22 pages, 3103 KiB  
Article
Genomic and Metabolomic Analysis of the Endophytic Fungus Alternaria alstroemeriae S6 Isolated from Veronica acinifolia: Identification of Anti-Bacterial Properties and Production of Succinic Acid
by Farkhod Eshboev, Alex X. Gao, Akhror Abdurashidov, Kamila Mardieva, Asadali Baymirzaev, Mirzatimur Musakhanov, Elvira Yusupova, Shengying Lin, Meixia Yang, Tina T. X. Dong, Shamansur Sagdullaev, Shakhnoz Azimova and Karl W. K. Tsim
Antibiotics 2025, 14(7), 713; https://doi.org/10.3390/antibiotics14070713 - 16 Jul 2025
Viewed by 440
Abstract
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 [...] Read more.
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
(This article belongs to the Section Fungi and Their Metabolites)
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18 pages, 8219 KiB  
Article
From Lebanese Soil to Antimicrobials: A Novel Streptomyces Species with Antimicrobial Potential
by Razane Hamiyeh, Aya Hanna and Antoine Abou Fayad
Fermentation 2025, 11(7), 406; https://doi.org/10.3390/fermentation11070406 - 15 Jul 2025
Viewed by 488
Abstract
The ongoing threat of antimicrobial-resistant pathogens has intensified the need for new antimicrobial agents, making the discovery of novel natural products crucial. This study focuses on the isolation and characterization of a novel Streptomyces species from the Anjar region in Lebanon, an area [...] Read more.
The ongoing threat of antimicrobial-resistant pathogens has intensified the need for new antimicrobial agents, making the discovery of novel natural products crucial. This study focuses on the isolation and characterization of a novel Streptomyces species from the Anjar region in Lebanon, an area rich in microbial diversity that is largely unexplored for its biotechnological potential. Soil samples were collected and processed, leading to the isolation of Streptomyces strain ANJ10. Comprehensive morphological, physiological, and genomic analyses were conducted, including whole-genome sequencing (WGS) to identify biosynthetic gene clusters (BGCs) and broth microdilution (BMD) assays to evaluate antimicrobial activity. The ANJ10 genome revealed 42 BGCs, significantly more than the average number in Streptomyces species, suggesting a high potential for secondary metabolite production. Phylogenetic analysis confirmed ANJ10 as a novel species, and BMD assays demonstrated its strong antimicrobial activity against several gram-negative pathogens, specifically, Acinetobacter baumannii. These findings underscore the potential of this strain as a significant source of new antimicrobial compounds, reinforcing the importance of exploring underexploited environments like Lebanon for microbial bioprospecting. Full article
(This article belongs to the Section Microbial Metabolism, Physiology & Genetics)
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19 pages, 7706 KiB  
Article
Genomic Insights into Vaccinium spp. Endophytes B. halotolerans and B. velezensis and Their Antimicrobial Potential
by Ingrida Mažeikienė, Birutė Frercks, Monika Kurgonaitė, Neringa Rasiukevičiūtė and Irena Mačionienė
Int. J. Mol. Sci. 2025, 26(14), 6677; https://doi.org/10.3390/ijms26146677 - 11 Jul 2025
Viewed by 258
Abstract
Plant microbiota contributes to nutrient absorption, and the production of hormones and vitamins, and plays a crucial role in responding to environmental stress. We hypothesized that Vaccinium spp. harbour a unique microbiota that enables them to coexist in extreme environments such as saline, [...] Read more.
Plant microbiota contributes to nutrient absorption, and the production of hormones and vitamins, and plays a crucial role in responding to environmental stress. We hypothesized that Vaccinium spp. harbour a unique microbiota that enables them to coexist in extreme environments such as saline, nutrient-poor, and waterlogged conditions. Upon examining Bacillus spp. endophytes isolated from blueberries, cranberries and lingonberries in vitro, we identified B. halotolerans (Bil-LT1_1, Bil-LT1_2) and B. velezensis (Cran-LT1_8, Ling-NOR4_15) strains that inhibit the growth of five pathogenic fungi and five foodborne bacteria. Whole-genome sequencing provided insights into genome organization and plasticity, helping identify mobile elements and genes potentially acquired through horizontal gene transfer. Functional annotation identified genes associated with plant colonization, stress tolerance, biocontrol activity, and plant growth promotion. Comparative genomic analyses revealed key biosynthetic gene clusters (BGCs) responsible for producing antifungal metabolites, including lipopeptides and polyketides. Genes supporting plant nutrition, growth, and environmental adaptation were present also in these strains. Notably, isolated endophytes exhibited particularly high levels of genomic plasticity, likely due to horizontal gene transfer involving gene ontology (GO) pathways related to survival in polymicrobial and foreign environments. Full article
(This article belongs to the Special Issue Microbial Omics: Decoding Microbial Life)
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12 pages, 4263 KiB  
Article
Characterization of a Novel Lentzea Species Isolated from the Kumtagh Desert and Genomic Insights into the Secondary Metabolite Potential of the Genus
by Ying Wen, Jiahui Li, Fujun Qiao, Wanyin Luo, Tuo Chen, Guangxiu Liu and Wei Zhang
Microorganisms 2025, 13(7), 1628; https://doi.org/10.3390/microorganisms13071628 - 10 Jul 2025
Viewed by 307
Abstract
A novel actinobacterial strain, designated E54T, 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 E54T within the genus Lentzea, [...] Read more.
A novel actinobacterial strain, designated E54T, 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 E54T within the genus Lentzea, showing highest similarity to Lentzea waywayandensis DSM 44232T (98.9%) and Lentzea flava NBRC 15743T (98.5%). However, whole-genome comparisons revealed that the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between E54T and these related strains were below the thresholds for species delineation. Strain E54T 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-C16:0. 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 E54T 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 E54T as a novel species. The strain E54T (=JCM 34936T = GDMCC 4.216T) should represent a novel species, for which the name Lentzea xerophila sp. nov. is proposed. Full article
(This article belongs to the Section Environmental Microbiology)
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15 pages, 1616 KiB  
Article
ScnR1-Mediated Competitive DNA Binding and Feedback Inhibition Regulate Guvermectin Biosynthesis in Streptomyces caniferus
by Haoran Shi, Jiabin Wang, Xuedong Zhang, Na Zhou, Xiangjing Wang, Wensheng Xiang, Shanshan Li and Yanyan Zhang
Biology 2025, 14(7), 813; https://doi.org/10.3390/biology14070813 - 4 Jul 2025
Viewed by 228
Abstract
Guvermectin, a Streptomyces-derived purine nucleoside compound, exhibits dual bioactivities as a plant growth regulator and an antibacterial agent. While its biosynthetic gene cluster (BGC) is regulated by the cluster-situated activator GvmR and the adjacent repressor GvmR2, the role of distal transcriptional regulators [...] Read more.
Guvermectin, a Streptomyces-derived purine nucleoside compound, exhibits dual bioactivities as a plant growth regulator and an antibacterial agent. While its biosynthetic gene cluster (BGC) is regulated by the cluster-situated activator GvmR and the adjacent repressor GvmR2, the role of distal transcriptional regulators (TRs) in guvermectin biosynthesis remains unexplored. Here, we identified ScnR1, a highly conserved LacI-family TR located far from the guvermectin BGC, which is directly activated by GvmR. Overexpression of scnR1 significantly suppressed guvermectin biosynthesis. Further investigations revealed that ScnR1 competitively binds to the gvmR, gvmA, and O1 promoters (overlapping with the GvmR-binding sites), thereby inhibiting the guvermectin BGC transcription. Moreover, ScnR1 formed a reciprocal feedback loop with the adjacent repressor GvmR2, where each repressor inhibits the other’s expression. These findings reveal a multi-layered regulatory mechanism wherein LacI-family TRs fine-tune guvermectin biosynthesis through competitive DNA binding and reciprocal feedback control. This study offers new perspectives on the hierarchical control of secondary metabolism in Streptomyces and provides valuable theoretical guidance for the engineering of strains with enhanced natural product production. Full article
(This article belongs to the Section Microbiology)
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11 pages, 1286 KiB  
Article
Evidence for Divergence of the Genus ‘Solwaraspora’ Within the Bacterial Family Micromonosporaceae
by Hailee I. Porter, Imraan Alas, Nyssa K. Krull, Doug R. Braun, Scott R. Rajski, Brian T. Murphy and Tim S. Bugni
Microorganisms 2025, 13(7), 1576; https://doi.org/10.3390/microorganisms13071576 - 4 Jul 2025
Viewed by 375
Abstract
The purpose of this study was to investigate the taxonomic and phylogenomic placement of the proposed genus ‘Solwaraspora’ within the context of other marine genera using a dual-omics approach. Initially, we isolated bacteria from marine tunicates, squirts, and sponges, which were [...] Read more.
The purpose of this study was to investigate the taxonomic and phylogenomic placement of the proposed genus ‘Solwaraspora’ within the context of other marine genera using a dual-omics approach. Initially, we isolated bacteria from marine tunicates, squirts, and sponges, which were morphologically similar to an emerging genus (identified as ‘Micromonospora_E’ by the GTDB-tk2 database using whole genome sequence data) by colony shape, size, and clustering pattern, but only found five strains in our dataset belonging to this distinction. Due to the minimally explored nature of this genus, we sought to identify more bacterial strains with similar morphology to MicromonosporaMicromonospora_E’ by whole genome sequencing (WGS). Within our collection, we noted 35 strains that met this criterion and extracted genomic information to perform WGS on these strains. With this information, we studied taxonomic and phylogenomic relationships among these organisms. Using the data gathered from WGS, we were able to identify an additional five strains labeled by the GTDB-tk2 database as MicromonosporaMicromonospora_E’, as well as construct phylogenomic trees to examine the evolutionary relationships between these strains. ANI values were calculated between strains from our dataset and type strains of Micromonospora and Plantactinospora as well as against an outgroup Streptomyces strain. No type strains are available for ‘Solwaraspora’. Using MALDI-TOF MS, we positively identified ‘Solwaraspora’, which was supported by the phylogenomic tree showing MicromonosporaMicromonospora_E’ (‘Solwaraspora’) in a distinct clade from Plantactinospora and Micromonospora. Additionally, we discovered gene cluster families (GCFs) in alignment with genera, as well as a large representation of biosynthetic gene clusters (BGCs) coming from the ‘Solwaraspora’ strains. These findings suggest significant potential to discover novel chemistry from ‘Solwaraspora’, adding to the importance of investigating this new genus of bacteria. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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10 pages, 1001 KiB  
Article
Genome Mining Reveals a Sactipeptide Biosynthetic Cluster in Staphylococcus pseudintermedius
by Ola K. Elsakhawy and Mohamed A. Abouelkhair
Vet. Sci. 2025, 12(7), 635; https://doi.org/10.3390/vetsci12070635 - 2 Jul 2025
Viewed by 370
Abstract
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 [...] Read more.
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
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16 pages, 2501 KiB  
Article
Phenotypic Characterization and Whole-Genome Analysis Revealing the Promising Metabolic Potential of a Newly Isolated Streptomyces sp. CH6
by Chung Thanh Nguyen, Huong Thi Nguyen, Van Thi Hong Dao, Khanh Phuong Do and Thuy Thi Thu Ta
Appl. Sci. 2025, 15(13), 7126; https://doi.org/10.3390/app15137126 - 25 Jun 2025
Viewed by 348
Abstract
Streptomyces spp. are considered a prolific resource of bioactive and structurally diverse secondary metabolites for natural product drug discovery. In this study, 20 out of 56 actinomycetes from soils showed antibacterial activity against at least one tested bacterium. Among them, the CH6 isolate [...] Read more.
Streptomyces spp. are considered a prolific resource of bioactive and structurally diverse secondary metabolites for natural product drug discovery. In this study, 20 out of 56 actinomycetes from soils showed antibacterial activity against at least one tested bacterium. Among them, the CH6 isolate could be a potential source of antibacterial compounds, as indicated by inhibition zone diameters (11.1–32.0 mm) and MIC values (from 8 to 128 µg/mL) against microbial pathogens. The extract showed moderate antioxidant activity against DPPH, hydroxyl, and superoxide anion radicals. Notably, CH6 extract displayed strong inhibitory effects on cancer cells, including MCF-7, A549, HepG2, and HT29, with IC50 values ranging from 18.0 to 73.4 µg/mL, without cytotoxic activity against non-cancerous HEK-293 cells. The genome of CH6 consists of a 6,936,977 bp linear chromosome with a 73.0% GC content, 5831 protein-coding genes, and 13 biosynthetic gene clusters (BGCs). The highest dDDH and ANI values between CH6 and the most closely related type strain, Streptomyces evansiae DSM 41979T, were 45.8% and 92.6%, respectively, which suggests that CH6 is a novel species. Interestingly, cluster 2, with a size of 133,857 bp, comprised both guangnanmycin and scabichelin clusters, which have been reported for the first time. These findings showed that Streptomyces sp. CH6 could be a novel species and a producer of guangnanmycin and even new secondary metabolites, particularly those with antibacterial and anticancer activities. Full article
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30 pages, 3771 KiB  
Review
The Deep Mining Era: Genomic, Metabolomic, and Integrative Approaches to Microbial Natural Products from 2018 to 2024
by Zhaochao Wang, Juanjuan Yu, Chenjie Wang, Yi Hua, Hong Wang and Jianwei Chen
Mar. Drugs 2025, 23(7), 261; https://doi.org/10.3390/md23070261 - 23 Jun 2025
Viewed by 872
Abstract
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 [...] Read more.
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 article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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25 pages, 5008 KiB  
Review
Engineering of Global Transcriptional Regulators (GTRs) in Aspergillus for Natural Product Discovery
by Yujie Zhao, Qing Gong and Huawei Zhang
J. Fungi 2025, 11(6), 449; https://doi.org/10.3390/jof11060449 - 12 Jun 2025
Viewed by 2231
Abstract
The Aspergillus genus is an important group of filamentous fungi, and the various biological activities of its secondary metabolites (SMs) have great biosynthetic potential. Despite over 4200 SMs having been isolated from Aspergillus spp., their metabolic potential remains unexplored due to the presence [...] Read more.
The Aspergillus genus is an important group of filamentous fungi, and the various biological activities of its secondary metabolites (SMs) have great biosynthetic potential. Despite over 4200 SMs having been isolated from Aspergillus spp., their metabolic potential remains unexplored due to the presence of numerous silent biosynthetic gene clusters (BGCs) in their genomes. Fortunately, over the last two decades, the global transcriptional regulator (GTR) engineering strategy has emerged as a powerful tool for activating these cryptic BGCs in order to synthesize previously undiscovered SMs from Aspergillus spp. This review highlights recent advances in fungal GTR engineering techniques, the regulatory mechanisms of GTRs, and current challenges and future perspectives for their application in natural product discovery in the genus Aspergillus. Full article
(This article belongs to the Special Issue Fungal Biotechnology and Application 3.0)
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16 pages, 5768 KiB  
Article
Integrated Transcriptomics and Metabolomics Provide Insight into Degeneration-Related Molecular Mechanisms of Morchella importuna During Repeated Subculturing
by Wenyan Huo, Xuelian He, Yu Liu, Liguang Zhang, Lu Dai, Peng Qi, Ting Qiao, Suying Hu, Pengpeng Lu and Junzhi Li
J. Fungi 2025, 11(6), 420; https://doi.org/10.3390/jof11060420 - 30 May 2025
Viewed by 756
Abstract
This study investigated Morchella importuna strain degeneration during repeated subculturing and employed metabolomics, transcriptomics, and other techniques to explore its molecular mechanisms. Significant metabolic and transcriptional differences were observed between normal mycelia (NM) and degenerated mycelia (DG). Metabolomic analysis revealed 699 differentially expressed [...] Read more.
This study investigated Morchella importuna strain degeneration during repeated subculturing and employed metabolomics, transcriptomics, and other techniques to explore its molecular mechanisms. Significant metabolic and transcriptional differences were observed between normal mycelia (NM) and degenerated mycelia (DG). Metabolomic analysis revealed 699 differentially expressed metabolites (DEMs) that were predominantly enriched in secondary metabolite biosynthesis pathways, particularly flavonoids and indole alkaloids. Total flavonoid content was markedly higher in NM than in DG, with most flavonoid compounds showing reduced levels in degenerated strains. Transcriptomic profiling revealed 2691 differentially expressed genes (DEGs), primarily associated with metabolic pathways and genetic information processing. Integrated analysis showed that metabolic dynamics were regulated by DEGs, with pyruvate metabolism being significantly enriched. The FunBGCeX tool identified biosynthetic gene clusters (BGCs) in the M. importuna genome, highlighting the critical role of the non-reducing polyketide synthase (NR-PKS) gene in flavonoid biosynthesis. This gene exhibited significantly downregulated expression in DG strains. These findings indicate that M. importuna degeneration resulted from systemic dysregulation of gene expression networks and metabolic pathway reorganization. The results presented herein also provide theoretical insights into degeneration mechanisms and potential prevention strategies for this edible fungus. Full article
(This article belongs to the Special Issue Fungal Metabolomics and Genomics)
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