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PubMed2024

Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management.

Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of anti-inflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor since its cytoprotective functions are considered to be the principle cellular defense mechanism against exogenous and endogenous insults, such as xenobiotics and oxidative stress. However, hyperactivation of the Nrf2 pathway supports the survival of normal as well as malignant cells, protecting them against oxidative stress, and therapeutic agents. Plants possess a pool of secondary metabolites with potential chemotherapeutic/chemopreventive actions. Modulation of Nrf2/ARE and downstream activities in a Keap1-dependant manner, with the aid of plant-derived secondary metabolites exhibits promise in the management of brain tumors. Current article highlights the effects of Nrf2/Keap1/ARE cascade on brain tumors, and the potential role of secondary metabolites regarding the management of the same.

Animals↗
PubMed2026

Hybrid genome assembly of Penicillium oxalicum UV4 delineates cryptic secondary metabolite pathways and robust lignocellulolytic potential.

Penicillium oxalicum is a saprophytic fungus well-known for its hydrolytic potential; however, little is known about its metabolic flexibility and secondary metabolite biosynthesis, especially in isolates from underrepresented areas. In this study, we sequenced the genomic DNA of Penicillium oxalicum UV4 using Illumina and Oxford Nanopore platforms, generating a high-quality hybrid genome assembly of 30.28 Mb. The genome features 7,944 predicted genes (7,747 protein-coding sequences and 197 tRNAs) and demonstrates high completeness (99.0% BUSCO). Genomic analysis revealed 40 Biosynthetic Gene Clusters (BGCs), including distant orthologs of the Alternaria phytotoxin ACT-toxin II and the mycotoxin alternariol, as well as a putative clavaric acid-like biosynthetic cluster. Further investigation revealed an expanded CAZyme repertoire comprising 150 secreted proteins, featuring an AA16 lytic polysaccharide monooxygenase and putative multi-domain architectures, such as a pectin methylesterase-polygalacturonase fusion. This comprehensive genomic profiling highlights the dynamic metabolic capacity of P. oxalicum UV4, establishing it as a highly promising candidate for bio-refining studies and the discovery of cryptic bioactive metabolites.

Penicillium↗
PubMed2026

Secondary metabolite profiling of rare Micromonospora spp. from cold desert of NW Himalayas via multi-omics analysis.

INTRODUCTION: The genus Micromonospora is a prolific producer of specialized metabolites with pharmacological and agronomic relevance. Natural products derived from the genus Micromonospora have a distinctive chemical diversity and enormous therapeutic potential, thus represent a potential source for drugs and drug leads. OBJECTIVE: To explore the biosynthetic potential of four Micromonospora strains isolated from cold desert of NW Himalayas through genome mining and to correlate predicted biosynthetic gene clusters with chemical features detected by untargeted LC-HRMS metabolomics. METHOD: High-quality genomes were annotated for BGCs and matched against untargeted LC-HRMS features (peak picking, alignment, and annotation to chemical classes). Each isolate was grown in triplicate, and fermented broth was pooled for further metabolomic studies. RESULTS: By integrating genomic and metabolomic approaches, specialized biosynthetic gene clusters and strain-based putative metabolite classes were identified. LRS1 showed elevated xanthines (RiPP/siderophore), LRS3 had phenolic glycosides (hybrid PKS/NRPS), LRS4 showed 70-fold hydroxycinnamate enrichment (Type II PKS), and LRS5 displayed p-benzoquinone enrichment (Type III PKS). The metabolite profile of each strain aligned with its predicted biosynthetic gene cluster composition. CONCLUSION: Under a single growth regime, each Micromonospora strain exhibits a distinct metabolomic profile. This metabologenomics workflow can be further explored to isolate specialized metabolites with potential therapeutic and agricultural value.

Micromonospora↗
PubMed2026

The dirigent protein MsDIR6 functions in drought tolerance and modulates reactive oxygen species scavenging and secondary metabolite biosynthesis in alfalfa.

Alfalfa (Medicago sativa L.) is a globally significant forage crop essential for ensuring global food security. However, soil water deficit leads to a substantial decline in its yield, posing a severe threat to sustainable forage production. Dirigent (DIR) proteins play important roles in lignan biosynthesis and plant stress responses. Here, we identified 52 MsDIR genes in alfalfa through a genome-wide analysis, and screened MsDIR6 as a key candidate gene associated with drought tolerance. The results of qRT-PCR showed that MsDIR6 transcription was significantly induced by drought stress in alfalfa. MsDIR6 was preferentially expressed in roots and leaves, and its protein was localized in the nucleus and plasma membrane. Heterologous expression of MsDIR6 in yeast improved tolerance to mannitol-triggered osmotic stress. Heterologous overexpression of MsDIR6 in Arabidopsis significantly increased seed germination rate, seedling survival rate, and antioxidant capacity under drought stress, while improving leaf water-holding capacity by regulating stomatal movement. In transgenic alfalfa hairy roots, MsDIR6 alleviated drought-induced growth inhibition and enhanced reactive oxygen species (ROS) scavenging mediated by the antioxidant defense system under drought stress. Transcriptomic analysis revealed that MsDIR6 activated key genes in the phenylpropanoid and flavonoid biosynthesis pathways, which are crucial for ROS scavenging during drought adaptation. Additionally, we observed elevated flavonoid and lignin contents in MsDIR6-overexpressing alfalfa. Collectively, our findings offer novel insights into alfalfa's drought tolerance mechanisms and identify MsDIR6 as a promising genetic resource for molecular breeding strategies to improve this vital forage crop.

Alfalfa↗
PubMed2025

Broad-spectrum antibacterial and antibiofilm activity of dandelion endophytic bacteria against multidrug-resistant bacteria.

Microbial secondary metabolites have long served as a key source of natural product-based drugs. This study evaluates the antibacterial, antibiofilm, and antioxidant activities of endophytic bacteria derived from dandelion, focusing on their effects against multidrug-resistant (MDR) clinical isolates. In total, 33 endophytic bacteria strains were isolated from Taraxacum ohwianum, representing 15 genera. Among these, 13 exhibited antibacterial activity, with 6 demonstrating efficacy against MDR clinical isolates. The endogenous strain Bacillus velezensis DR8 showed strong antibacterial activity against all three MDR strains tested and exerted inhibitory effects on the biofilm formation and dispersal of methicillin-resistant Staphylococcus aureus. Genome sequencing and antibiotics and secondary metabolite analysis shell analysis revealed that this strain harbors 12 biosynthetic gene clusters (BGCs) associated with secondary metabolite production. Of these, seven BGCs exhibited ≥ 80% similarity to known clusters, suggesting the potential to synthesize surfactin, difficidin, fengycin, bacillaene, macrolactin H, bacilysin, and bacillibactin. Overall, these findings indicate that endophytic bacteria from dandelion are a potential source of antibacterial compounds and biofilm formation inhibitors.

Endophytes↗
PubMed2025

South African Myxococcota: an untapped resource for microbial ecolo gy and biotechnology.

An extraordinary multicellular life cycle, ecological versatility, and prolific production of bioactive secondary metabolites characterise the phylum Myxococcota. While research has predominantly focused on Myxococcota in Asia, Europe, and North America, their potential occurrence in Sub-Saharan Africa remains largely unexplored. To date, only one study has isolated Myxococcota in South Africa, with additional findings limited to incidental detection through metagenomic studies. Considering South Africa's ecological diversity, its biomes may represent promising but under-examined environments for systematic bioprospecting aimed at discovering novel Myxococcota with ecological or biotechnological potential. The recent reclassification of Myxococcota from the former Deltaproteobacteria has provided a more coherent taxonomic framework to guide future ecological and systematic studies. This review presents an overview of the taxonomic revision and explores the potential occurrence of Myxococcota in South African biomes. It covers the challenges associated with conventional culture-based isolation methods and highlights potential genome- and metagenome-based approaches, including the use of metagenome-assembled genomes (MAGs) to identify cryptic biosynthetic gene clusters (BGCs), while acknowledging current limitations. Considering the increasing resistance to chemical fungicides in South African agriculture, this review further explores the potential of Myxococcota-derived secondary metabolites as candidate bioprotective alternatives. By identifying current research gaps, it aims to support future efforts towards systematic bioprospecting to investigate the ecological and biotechnological potential of Myxococcota in South Africa. KEY POINTS: • South African biomes may harbour novel Myxococcota with biosynthetic potential. • Genome mining could reveal cryptic biosynthetic gene clusters (BGCs). • Myxococcota metabolites may help control resistant fungal phytopathogens.

South Africa↗
PubMed2025

Identification of an antifungal lipopeptide from Bacillus amyloliquefaciens HAU3 inhibiting the growth of Fusarium graminearum using preparative chromatography and 2D-NMR.

UNLABELLED: The presence of fungal contamination and its mycotoxins in animal feed is pervasive, posing a significant threat to the well-being and performance of animals, as well as the safety of animal-derived food products. In this work, we screened a strain of Bacillus amyloliquefaciens (B. amyloliquefaciens) HAU3 that exhibits efficient antifungal activity against the growth of Fusarium graminearum (F. graminearum). The antifungal activity was detected in the supernatant, with 20% sterile supernatant demonstrating an impressive antifungal rate of 98.46% against F. graminearum. The antifungal activity of the strain was evaluated through spectrum analysis and silage trials, revealing its effective antifungal activity against multiple fungal species. Furthermore, the strain is capable of degrading ZEN and its derivatives. The targeted disruption of fungal mycelial membrane was observed using scanning electron microscopy and transmission electron microscopy. Additionally, staining with the reactive oxygen species (ROS)-sensitive fluorogenic dye DCFH-DA and propidium iodide (PI) revealed that the strain induces accumulation of ROS in fungal mycelia. The active compounds underwent further separation, purification, and detection. The prominent active peak was identified through mass spectrometry and magnetic resonance spectroscopy. The molecular structure of the active compounds was predicted to be lipopeptides composed of 8 amino acids known as fengycin. The whole genome sequencing and informatics analysis unveiled a total of 13 gene clusters responsible for the synthesis of secondary metabolites. The antifungal effects of B. amyloliquefaciens HAU3 are exerted through the synthesis of fengycin, which selectively targets and compromises the integrity of fungal mycelia membranes, thereby making it a potential biocontrol agent for mitigating mycotoxin contamination in feed. IMPORTANCE: Mycotoxin contamination in animal feed, predominantly driven by Fusarium graminearum, represents a persistent threat to livestock health and food chain integrity. Here, we report the isolation of a soil-derived Bacillus amyloliquefaciens HAU3, exhibiting potent and broad-spectrum antifungal activity alongside efficient biodegradation of zearalenone and its derivatives. Mechanistic dissection reveals that fengycin, the principal bioactive metabolite, compromises fungal membrane integrity and elicits intracellular oxidative stress, culminating in hyphal collapse. Genomic profiling uncovers a diverse repertoire of biosynthetic gene clusters underpinning secondary metabolite production. These findings establish strain HAU3 as a promising microbial chassis for the development of next-generation biocontrol strategies aimed at mitigating mycotoxin burden in agroecosystems.

Bacillus amyloliquefaciens↗
PubMed2026

Heavy metal stress in native plant species: investigating phytoremediation potential through physiological and ISSR/SCoT molecular assessments.

In emerging countries, increased industrial activity has a significant impact on economic growth and urban development. However, the acceleration of industrial processes is accompanied by the release of contaminants such as heavy metals. According to the World Health Organization, one-fourth of all human diseases are caused by environmental contaminants, including heavy metals, which can impair numerous organs such as the neurological system, liver, and reproductive systems. This increased efforts to find effective and sustainable methods to remove heavy metals. Phytoremediation is an environmentally benign method of removing heavy metals using specific plants. Thus, from industrially contaminated locations, common native plant species of Lactuca serriola, Sisymbrium irio, Chenopodium murale, and Cynanchum acutum were selected for this study to assess the mechanisms of their molecular and physiological tolerance. Soil and plants were tested for heavy metals (Cd, Pb, and Cu), and contaminated locations were classified as low and highly polluted. Measurements were made of soluble sugar, protein, secondary metabolites, malondialdehyde, and H2O2. Additionally, inter simple sequence repeat (ISSR), start codon targeted (SCoT), and genomic template stability GTS were used. In heavily polluted areas, all plant species exhibit elevated amounts of sugar, proteins, H2O2, MDA, and secondary metabolites, while total phenolics showed a unique significant interaction (plant-location), where Cynanchum exhibited a hyper-stress phenolic accumulation to cope with toxicity, whereas Chenopodium maintained genomic stability with balanced phenolic level. Based on these findings, both Cynanchum acutum and Chenopodium murale demonstrate superior potential for phytoremediation and warrant further investigation for ecological restoration.

Heavy metal↗
PubMed2026

Addressing lignin composition and content via Arabidopsis arogenate dehydratase knockout and over-expression genotypes.

Following the down-selection of 14 Arabidopsis thaliana arogenate dehydratase (ADT) knockout and over-expression (OE) genotypes, the most highly contrasting quadruple knockout adt3/4/5/6 and ADT OE genotypes were subjected to proteomics, metabolomics, and scanning electron microscopy (SEM) analyses as needed, with results compared to Columbia wild-type (WT). The basal adt3/4/5/6 stem cross-sections, ∼70% lignin content reduced, exhibited buckled vessel cell walls and partially detached xylary fibers, in contrast to WT and ADT4m/5 m OE genotypes that did not. Anatomical defects primarily resulted from guaiacyl lignin level reductions in vessels with concomitant increased stem syringyl:guaiacyl (S/G) ratios. Phenylpropanoid and various upstream shikimate-chorismate pathway enzyme abundances, as well as specific monolignol oxidases (laccases/peroxidases), generally increased in adt3/4/5/6 at different stem and rosette leaf growth/development stages, relative to WT. Opposite effects were largely observed with the ADT5m OE genotype. By contrast, flavonoid and glucosinolate pathway enzyme amounts varied. Such enzyme abundance increases were overall unproductive as adt3/4/5/6 was unable to restore WT, ADT4 OE, ADT5 OE, ADT5m OE, and ADT4m/5 m OE secondary metabolite (lignin, phenylpropanoid, lignan, flavonoid, phenolic acid, and glucosinolate) levels. Conversely, ADT OE genotypes did not significantly increase programmed lignin levels or alter S/G compositions. In sum, proteomics analyses of adt3/4/5/6 and adt5 'perceived' that lignin and low molecular weight secondary metabolite amounts were not at 'programmed' levels as for WT and ADT OE genotypes but observed increases in relevant pathway protein abundances were futile. Notably though, proteomics analyses did not lead to predicting that lignin and associated biochemical pathways would have reduced metabolite levels, relative to WT and ADT OE genotypes. Genotype adt3/4/5/6, possibly the highest lignin level reduced genotype reported, did not utilize other phenolics to compensate. By contrast, the differential temporal and spatial deposition of cell wall oxidases again indicate the exquisite control over lignin deposition, and our lack of knowledge of precise lignin structure and assembly in subcellular regions of the lignified cell walls.

Lignin↗
PubMed2026

Whole-genome sequencing and analysis of the endophytic fungus Alternaria alternata Y-2 from Leymus chinensis.

To explore the genetic basis and functional potential of beneficial symbiosis between the endophytic fungus Alternaria alternata Y-2 and its host Leymus chinensis, we performed Illumina-based draft whole-genome sequencing and systematic bioinformatic analysis. Although this assembly does not reach telomere-to-telomere completeness, it provides high-quality gene-level information for gene prediction, functional annotation, carbohydrate-active enzyme (CAZyme) identification, and secondary metabolite biosynthetic gene cluster analysis. The final genome size of A. alternata Y-2 was 34,383,676 bp with a GC content of 51.0%, containing 12,724 predicted protein-coding genes, 90 tRNAs, and 12 rRNAs. BUSCO assessment showed 98.9% completeness, supporting the high quality of this draft genome. A total of 12,627 genes were successfully annotated in the NCBI NR database, and 17,183 genes were functionally categorized using GO terms. In total, 448 CAZyme genes and 21 secondary metabolite biosynthetic gene clusters were identified, which are potentially involved in lignocellulose degradation, cellular redox homeostasis and biosynthesis of bioactive metabolites. Based on ITS sequence alignment, NR annotation, and phylogenetic analysis of single-copy orthologous genes, the strain was confidently identified as A. alternata. This study firstly reports the draft genome of an endophytic A. alternata strain derived from L. chinensis and provides valuable genetic resources for exploring the endophytic lifestyle, stress tolerance, and bioactive metabolite potential of this fungus.

Alternaria↗
PubMed2026

Integrated functional genomics and safety assessment of plant-growth-promoting Caryophanales from post-maize-cultivation soils.

This study aimed to evaluate six environmental bacterial strains isolated from post-maize cultivation soils as candidates for agricultural biopreparation development, using an integrated functional genomic and safety assessment framework. Building on experimental validation of plant-growth-promoting activities, the analysis included: plant-growth-promoting traits (PGPT-Pred) using PLABase; carbohydrate-active enzymes (CAZymes) relevant for lignocellulosic crop residue degradation (dbCAN3); secondary metabolite profiles (antiSMASH); and screening for virulence factors and antibiotic resistance genes (ABRicate, BTyper3).All analyzed strains possess 1,449-1,617 predicted PGPT-encoding genes (24.1-35.9% of total genes), which are strongly shaped by taxonomic relatedness, as confirmed by congruence testing against ANI-based genomic divergence. Paenibacillus amylolyticus 5mez and Priestia megaterium 7psych showed distinct functional profiles compared to Bacillus spp., while Bacillus subtilis sensu lato strains were most similar to each other. Genomic predictions suggest involvement in nutrient acquisition (N, P, K, Fe) and stress mitigation. Secondary metabolite analysis revealed high biosynthetic potential, with non-Bacillus species harbouring a large proportion of unknown gene clusters, indicating underexplored metabolite diversity. CAZyme profiling identified P. amylolyticus 5mez as the most enzyme-rich strain, while B. cereus s.s. zielonkawy showed ligninolytic potential despite low overall CAZyme abundance. The safety assessment identified B. cereus s.s. zielonkawy as toxigenic and unsuitable for use. Of the remaining strains, P. amylolyticus 5mez and Pr. megaterium 7psych demonstrated the most favourable safety profiles, exhibiting no detectable virulence factors or antibiotic resistance genes, justifying their priority use in agricultural biopreparations, pending phenotypic validation. Given the high-dimensional, low-sample-size nature of multi-trait datasets in applied microbial genomics, tailored statistical approaches, including noise-reduction-validated PCA and distance-based congruence testing, were applied; their rationale and limitations are discussed.

Soil Microbiology↗
PubMed2026

Transcriptome analysis of brown adipose tissue in Brandt's vole treated with tannic acid under cold exposure.

BACKGROUND: Tannic acid (TA) is a hydrolysable plant secondary metabolite known to influence multiple physiological processes in animals; however, its role in regulating brown adipose tissue (BAT) thermogenesis remains poorly understood. Notably, the overwinter food caches of Brandt's voles predominantly consist of Artemisia species, which are rich in TA. This study aimed to determine whether TA contributes to cold tolerance in Brandt's voles by activating BAT thermogenesis. Adult male voles were administered TA, after which the masses of BAT and inguinal white adipose tissue (iWAT) were measured, and temperature changes in BAT, the body surface, and the rectum were recorded following exposure to - 20 °C. In addition, transcriptomic analyses of BAT were performed, and the expression and protein levels of key thermogenic markers were assessed. RESULTS: The results showed that TA reduced iWAT mass while exerting minimal effects on BAT mass. TA-treated voles exhibited significantly elevated temperatures in BAT, the body surface, and the rectum after cold exposure. Histological analyses revealed that TA treatment reduced adipocyte area in iWAT while increasing the number of nuclei in brown adipocytes in BAT. In BAT, differentially expressed genes (DEGs) in voles receiving a low TA dose were significantly enriched in pathways related to fat digestion and absorption and peroxisome proliferator-activated receptor (PPAR) signaling. In contrast, DEGs in voles administered a high TA dose were predominantly associated with brown adipocyte differentiation and the upregulation of cold-induced thermogenesis. Moreover, TA administration increased the expression of FFAR4 and UCP1, as well as the protein levels of PGC-1α, PPARγ, and UCP1 following cold exposure. CONCLUSIONS: Collectively, these findings demonstrate that TA enhances cold tolerance in Brandt's voles by promoting thermogenic gene expression and stimulating brown adipocyte differentiation in BAT, providing novel insights into the role of plant secondary metabolites in mammalian cold adaptation and herbivore-plant interactions.

Animals↗
PubMed2026

DeepMASS v.2: An enhanced deep learning platform for large-scale discovery and structural annotation of unknown plant metabolites.

Determining the structures of unknown metabolites remains a fundamental bottleneck in plant metabolomics, as the vast chemical diversity of plant secondary metabolites far exceeds the coverage of existing spectral libraries. Here, we present DeepMASS v.2, a substantially enhanced platform for annotating unknown metabolites from liquid chromatography-tandem mass spectrometry data, designed to address this challenge at scale. DeepMASS v.2 leverages a semantic spectral representation model trained on millions of spectra from GNPS, NIST, and in-house resources. By integrating Spec2Vec-based embeddings with HNSW (hierarchical navigable small world) graph retrieval and a unified chemical space defined by molecular fingerprints, DeepMASS v.2 identifies structurally related neighbors of unknown spectra and ranks candidate structures according to their proximity to the predicted structural neighborhoods within chemical space. Benchmarking against Critical Assessment of Small Molecule Identification datasets and a curated natural product collection demonstrated that DeepMASS v.2 outperforms state-of-the-art in silico annotation tools, including SIRIUS, CFM-ID, MetFrag, and MS-Finder. Importantly, DeepMASS v.2 maintains strong performance for metabolites absent from spectral libraries, highlighting its capacity to annotate genuinely unknown compounds. Application of DeepMASS v.2 to large-scale plant metabolomics datasets demonstrated its ability to expand accessible metabolome coverage. Implemented as an intuitive web platform, DeepMASS v.2 provides the community with a scalable, interpretable, and high-throughput solution for structural annotation, enabling more comprehensive characterization of plant chemical diversity and accelerating natural product discovery in molecular plant science. The DeepMASS v.2 web server is publicly available at http://deepmass.cn.

Metabolomics↗
PubMed2025

Marine endophytes: biosynthetic engines for novel bioactive metabolites.

Marine endophytes are prolific sources of structurally diverse secondary metabolites with significant pharmaceutical potential, including anticancer, antimicrobial, and antioxidant agents. However, their commercial utilization is hindered by genomic instability in axenic cultures and inconsistent metabolite yields. While current studies focus on symbiotic interactions and compound discover, critical gaps persist in harnessing their biosynthetic capabilities. This review synthesizes knowledge on marine fungal metabolites and proposes a paradigm shift toward resource-driven research. It addresses strain improvement limitations and suggests strategies like mutagenesis, protoplast fusion, and metabolic engineering to bolster production stability and efficiency. The paper also discusses biological process optimization, including fermentation tuning, inducer and precursor addition, and adsorbent use, to enhance natural product synthesis. By identifying these research gaps and proposing a strategic roadmap, the review advances the stable and scalable production of bioactive metabolites, unlocking the commercial and therapeutic potential of marine endophytic fungi.

bioactive metabolites↗
PubMed2026

Draft genome sequence data of Streptomyces antibioticus SCBA4 isolated from the Soils of Surigao del Sur, Philippines.

The draft genome of Streptomyces antibioticus SCBA4 isolated from the soils of Surigao del Sur, Philippines is reported here. S. antibioticus is a member of the phylum Actinomycetota, a diverse group of Gram positive, high G+C content bacteria well known for their production of a variety of bioactive compounds. Sequencing using the Illumina NovaSeq 6000 platform yielded a 8,616,999 bp genome across 36 contigs with 7621 coding sequences, 87 tRNA, and 1 tmRNA. Consistent with the members of the same phylum, the GC content was 71.83% and was found to contain putative gene clusters of secondary metabolites such as NRPs, terpenes and polyketides. The genome sequence has been deposited at NCBI under the accession number JBSWZT020000000.

Actinobacteria↗
PubMed2025

Biosynthetic potential of the culturable foliar fungi associated with field-grown lettuce.

Fungal endophytes and epiphytes associated with plant leaves can play important ecological roles through the production of specialized metabolites encoded by biosynthetic gene clusters (BGCs). However, their functional capacity, especially in crops like lettuce (Lactuca sativa L.), remains poorly understood. We sequenced the genomes of nine fungal isolates, representing Fusarium sp., Fulvia sp., Alternaria alternata, and Alternaria postmessia, from leaves of lettuce grown under field conditions in Arizona, USA. We used antibiotics and secondary metabolite analysis shell (antiSMASH) and the database for automated carbohydrate-active enzyme annotation (dbCAN3), to predict BGCs and carbohydrate-active enzymes (CAZymes) for each strain, and then compared them to conspecific strains from other environments and substrates. Foliar lettuce-associated fungi featured 39-95 BGCs per genome, with substantial overlap between isolates occurring in association with lettuce leaves vs. from other substrates. Species identity was a significant determinant of BGC count, while host type, isolation source, and lifestyle were not. Several BGCs, including those for alternariol and 1,3,6,8-Tetrahydroxynaphthalene (T4HN), showed 100% similarity to characterized minimum information about a biosynthetic gene cluster (MIBiG) clusters based on antiSMASH predictions. Although analysis by biosynthetic gene similarity clustering and prospecting engine (BiG-SCAPE) identified gene cluster families (GCFs) across the dataset, these reference-matching clusters were not always grouped, reflecting methodological differences in how the tools assess similarity. Comparative CAZyme analysis in a focal species (Fulvia sp.) revealed higher gene counts in a foliar lettuce-derived isolate than in tomato (Solanum lycopersicum)-associated strains, challenging assumptions about host chemical complexity. These results highlight the importance of phylogenetic context in shaping fungal functional potential and suggest that selection on microbial traits in edible leafy crops may be more subtle and species-specific than previously assumed. KEY POINTS: • Lettuce-associated fungi feature diverse biosynthetic potential • Phylogeny predicts fungal BGC content more strongly than ecological lifestyle • Findings support genome-informed microbiome strategies for leafy crops.

Lactuca↗
PubMed2026

Draft genome sequences of three Bacillus spp. from the University of the Philippines Culture Collection.

This study reports the assembled and annotated draft genomes of three Bacillus spp. isolates from the University of the Philippines Culture Collection. Genome analysis predicted genes for stress tolerance, plant-growth promotion, and secondary metabolite production, highlighting their potential for diverse biotechnological applications in agriculture and natural product synthesis.

Bacillus↗
PubMed2026

Comparative genomics reveals hidden biosynthetic diversity in Streptomyces spp. and metal-dependent regulatory features associated with untapped specialized metabolites.

The genus Streptomyces is one of the richest sources of bioactive natural products; however, a substantial proportion of its biosynthetic gene clusters (BGCs) remain cryptic and their metabolic products are unresolved. Advances in genome mining and computational prediction now enable comprehensive exploration of this hidden biosynthetic repertoire. In this study, whole-genome sequencing and comparative genomic analyses were performed on three three newly isolated Streptomyces strains to evaluate their specialized metabolic potential. Genome assemblies were annotated and systematically analyzed using antiSMASH, DeepBGC, GECCO, and PRISM to identify, cross-validate, and functionally characterize BGCs while predicting their associated secondary metabolite scaffolds. Taxonomic analyses based on Average Nucleotide Identity (ANI), phylogenomics, and BLAST identified the isolates as Streptomyces thinghirensis, Streptomyces novocaesareae, and Streptomyces griseorubens. Applying the consensus framework across the three Streptomyces genomes yielded 43 cryptic BGCs, lacking close similarity to reference BGCs in the MIBiG database, of which 26 were classified as HIGH, 10 as MEDIUM, and 7 as LOW confidence. Notably, numerous BGCs exhibited low abundance to characterized reference clusters, indicating a high potential for previously undescribed biosynthetic pathways and novel metabolite scaffolds. Comparative analyses further revealed strain-specific biosynthetic architectures together with putative metal-responsive regulatory systems; Fur, Zur, and Nur, which were frequently associated with specialized metabolite biosynthetic loci. Collectively, these findings demonstrate the effectiveness of integrated genome-mining strategies for prioritizing cryptic biosynthetic gene clusters and highlight the remarkable biosynthetic potential of newly identified Streptomyces isolates as a source of novel natural products.

comparative genomics↗