Search Results (128)

This experiment aimed to investigate the metabolism of L-Citrulline (L-Cit) in the intestinal tract of ewes and its effects on fecal microbiota composition, plasma metabolism, and reproductive hormone levels. Twelve 18-month-old non-pregnant multiparous Turpan black ewes weighing 51.65 kg ± 2.49 kg were selected and randomly assigned to a control group (Con) and an experimental group (L-Cit), with six ewes in each group. Both groups were fed identical nutrient-dense rations. In the Con group, 100 mL of saline was administered through the duodenal fistula, while the L-Cit group received an additional 0.25 g/kg BW⁻¹ of L-Cit solution. On day 7, the crude protein and amino acid concentrations in feces and urine were assessed using total feces and urine collection methods. Fecal and blood samples were collected to evaluate microbiological and reproductive hormone indices, with blood samples also collected for plasma non-targeted metabolomics analysis two hours post-infusion. Compared to the Con group, the L-Cit group exhibited a significant reduction in crude protein content in feces (p < 0.05) and a highly significant decrease in urine (p < 0.01). Nitrogen metabolism indices did not differ significantly between groups (p > 0.05), but the L-lysine content in feces was significantly higher in the L-Cit group (p < 0.05). 16S rRNA sequencing revealed no significant PCA separation between the two groups. However, the relative abundance of Lachnospiraceae_NK3A20_group, Oscillibacter, and Mogibacterium was significantly higher in the Con group (p < 0.01), while SP3-e08, Parvibacter, Anaerosporobacter, Butyricimonas, and Peptococcus were more abundant in the L-Cit group (p < 0.05). LC-MS analysis showed significant up-regulation of purine and nucleotide metabolism pathways in the L-Cit group (p < 0.05). Plasma levels of estradiol (E₂), progesterone (P₄), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were significantly elevated in the L-Cit group at both 1 and 2 h post-infusion (p < 0.01). These results suggest that duodenal infusion of L-Cit enhances intestinal nitrogen utilization, alters specific bacterial populations, promotes purine and nucleotide metabolism, and stimulates reproductive hormone secretion in ewes. Full article

Background: Systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) is the leading cause of morbidity and mortality in patients with SSc, with an unmet need for validated, minimally invasive biomarkers for early detection. Extracellular vesicles (EVs) present underexplored pathogenic players and potential biomarker sources in SSc-ILD. We performed a proteomic shotgun study aiming to identify disease-specific protein signatures and potential biomarker candidates. Methods: The study included 30 SSc patients divided into SSc-ILD and SSc w/o ILD groups and 20 matched controls. Plasma-derived EV-enriched fractions were analysed using liquid chromatography–mass spectrometry. Bioinformatic analysis, including differentially expressed proteins (DEPs), functional enrichment, protein–protein interaction network and Markov Cluster (MCL) analysis was performed. Results: Analysis of DEPs showed 14 significantly upregulated and 1 downregulated protein when comparing the SSc-ILD to the SSc w/o ILD group, 222 upregulated and 257 downregulated proteins between the SSc-ILD and control group, as well as 362 upregulated and 492 downregulated proteins between the SSc w/o ILD and control group. Functional enrichment analysis and MCL analysis pointed to disease-specific processes of extracellular matrix (ECM) and immune dysregulation, which largely overlapped between SSc-ILD and SSc w/o ILD groups. Among identified DEPs, SP-B, Cav-1 and Siglec-5 emerged as potential candidate biomarkers for SSc-ILD. Conclusions: Proteomic analysis of plasma-derived EV-enriched fractions shows potential EV involvement in pathogenic SSc processes, mainly related to ECM and immune dysregulation, as well as potential candidate biomarkers for SSc-ILD. Further studies are required to validate these results and assess biomarker potential and translational applicability of identified proteins. Full article

Chronic kidney disease (CKD) affects approximately 700 million people worldwide and is a major contributor to end-stage renal disease (ESRD), cardiovascular morbidity, and premature mortality. Although oxidative stress has long been considered central to CKD progression, conventional antioxidant strategies have not consistently improved clinical outcomes, suggesting that excess reactive oxygen species (ROS) alone cannot fully account for the underlying disease pathophysiology. Emerging evidence supports a broader paradigm of redox network failure, characterized by the disruption of coordinated signaling among ROS, nitric oxide (NO), and reactive sulfur species (RSS). Within this framework, hydrogen sulfide (H₂S), a major endogenous RSS, functions as a key regulator of renal redox homeostasis. CKD is consistently associated with systemic and renal H₂S deficiency, accompanied by downregulation of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as impaired transsulfuration and disrupted mitochondrial sulfide oxidation. Importantly, this deficiency cannot be explained solely by reduced renal function but instead reflects active suppression of H₂S biosynthesis. Uremic toxins, particularly indoxyl sulfate (IS), contribute to this process through activation of the aryl hydrocarbon receptor (AhR), which inhibits specificity protein 1 (Sp1)-dependent transcription of H₂S-producing enzymes. This IS–AhR–Sp1 axis provides a mechanistic link between toxin accumulation and disruption of the sulfur arm of the redox network, amplifying oxidative stress, endothelial dysfunction, mitochondrial impairment, ferroptotic vulnerability, and fibrotic remodeling. Beyond H₂S itself, downstream RSS, including persulfides, polysulfides, and thiosulfate, may represent the principal bioactive mediators of sulfur-dependent redox signaling, and their coordinated depletion in CKD may impair redox buffering capacity beyond what H₂S measurement alone reflects. This review integrates current evidence to propose a conceptual model in which CKD progression involves failure of coordinated redox signaling—characterized by feed-forward network collapse and threshold-dependent transition to a self-sustaining high-ROS state—with H₂S deficiency representing one mechanistically supported component of this broader network disruption. This framework highlights the therapeutic potential of targeting redox network restoration rather than isolated oxidative pathways in CKD. Full article

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy characterized by poor prognosis and limited therapeutic response. Cancer stem cells (CSCs) contribute to tumor progression, therapeutic resistance, and tumor recurrence. Among transcriptional regulators potentially involved in these processes, Specificity Protein 1 (SP1) has emerged as a candidate integrator of oncogenic and epigenetic signaling networks. However, its contribution to CSC-associated phenotypes and drug resistance in HCC remains incompletely defined. In this study, we combined transcriptomic analyses of TCGA datasets with functional experiments in HCC cell lines (Huh7 and HepG2). SP1-associated transcriptional programs were targeted pharmacologically using mithramycin A (MIT-A) and genetically using siRNA-mediated knockdown. The effects were assessed by RNA sequencing, RT-qPCR, Western blotting, flow cytometry, and functional assays evaluating proliferation, migration, CSC-associated properties, and response to sorafenib. MIT-A treatment markedly reduced the expression of stemness-associated transcription factors (NANOG, OCT4, SOX2) and CSC markers (CD133, CD24), impaired CSC-related functions including ALDH activity and the Side Population phenotype, and inhibited cell proliferation and migration. MIT-A also sensitized both parental and sorafenib-resistant HCC cells to sorafenib, associated with modulation of apoptotic regulators and reduced transporter-mediated efflux activity. SP1 knockdown partially reproduced several of these effects, supporting a contribution of SP1-dependent transcriptional programs to these phenotypes. Overall, these findings identify SP1-associated transcriptional networks as potential regulators of CSC features and therapeutic resistance in HCC and support targeting SP1-associated transcriptional programs as a strategy to enhance sorafenib efficacy. Full article

Microalgae and cyanobacteria represent an emerging and sustainable source of bioactive compounds for the food, cosmeceutical, and pharmaceutical sectors. In this study, the potential of two microalgae-cyanobacteria consortia, consortium 1 (C1) consisting of Chlorella vulgaris and Arthrospira platensis, and consortium 2 (C2) consisting of Kamptonema sp., Nannochloropsis oculata, Tetraselmis suecica, and Chlorella vulgaris, as a source of bioactive peptides was evaluated. Firstly, protein extraction from both biomasses was optimized by testing different protein solubilization and precipitation pHs, with pH 10 and pH 5 providing the best results in terms of protein recovery in both cases. Selected protein extracts, with protein contents of 28.50 ± 2.69% (C1) and 8.46 ± 0.45% (C2), were further hydrolyzed with Alcalase, evaluating the impact of the incubation time on peptide release and the antioxidant capacity of hydrolysates. A total of 1 h of hydrolysis proved to be enough for antioxidant capacity increase. In addition, in silico hydrolysis of the proteins identified with Alcalase in C1 and C2 (data are available via ProteomeXchange with identifier PXD077201 and PXD077149 for C1 and C2, respectively) was evaluated, assessing the potential bioactivity of the peptides produced, more specifically their antioxidant capacity. Our findings demonstrate that both microalgae-cyanobacteria consortia are valuable sources of bioactive compounds with antioxidant capacity, with potential interest as functional ingredients for the food, cosmeceutical, and pharmaceutical industries. Full article

Three previously uncharacterized lactones, namely penicianstinoid L (1), talaromyketide J (2) and peniciisocoumarin K (3), along with twenty-eight known compounds (4–31), were yielded from the mangrove-derived fungus Talaromyces sp. SCSIO41445, collected from Mangrove Park (NARA), Sri Lanka. Their structures were established by HRESIMS and NMR spectroscopic analysis (including ¹H and ¹³C NMR, HSQC, and HMBC), with the stereostructures of 2 and 3 being confirmed by single-crystal X-ray crystallographic analysis. Furthermore, compounds 1–31 were evaluated in terms of their neuraminidase (NA) inhibitory activities. These bioassay results revealed that three lactones (11, 15, and 16) of them exerted NA inhibitory effects, with IC₅₀ values of 46.66 ± 2.31, 20.78 ± 1.89, and 34.14 ± 2.56 µM, respectively. Moreover, molecular docking analysis demonstrated the potential of these compounds to inhibit NA enzymes, revealing specific interactions between the compounds and target proteins. Full article

The escalating global demand for large-scale, cost-effective, and sustainable high-quality protein has positioned single-cell protein (SCP) production from one-carbon (C1) gases as a highly promising solution. In this study, eight chemolithoautotrophic hydrogen-oxidizing bacteria (HOB) were isolated from mangrove sediments. Based on the 16S rRNA gene sequence analysis, they belonged to genera Sulfurimonas, Sulfurovum, Thiomicrolovo, and Marinobacterium. Among these, Thiomicrolovo sp. ZZH C-3 was identified as the most promising candidate for SCP production based on the highest biomass and protein content, and was selected for further characterization. Strain ZZH C-3 is a Gram-negative, short rod-shaped bacterium with multiple flagella. It can grow chemolithoautotrophically by using molecular hydrogen as an energy source and molecular oxygen as an electron acceptor. Genomic analysis further confirmed that ZZH C-3 harbors a complete reverse tricarboxylic acid (rTCA) cycle gene set for carbon fixation, and diverse hydrogenases (Group I, II, IV) for hydrogen oxidation. Subsequently, its cultivation conditions and medium composition for SCP production were systematically optimized using single-factor experiments and response surface methodology (RSM). Results showed that the optimal growth conditions were 28 °C, pH 7.0, and with 1 g/L (NH₄)₂SO₄ as the nitrogen source, 5–10% oxygen concentration, 9.70 mg/L FeSO₄·7H₂O, 0.17 g/L CaCl₂·2H₂O, and 1.90 mg/L MnSO₄·H₂O. Under the optimized conditions, strain ZZH C-3 achieved a maximum specific growth rate of 0.46 h⁻¹. After 28 h of cultivation, the optical density at 600 nm (OD₆₀₀) reached 0.94, corresponding to a biomass concentration of 0.60 g/L, and the protein content ranked at 73.56%. The biomass yield on hydrogen (Y_H2) was approximately 3.01 g/g H₂, with an average H₂-to-CO₂ consumption molar ratio of about 3.78. Compared to the model HOB Cupriavidus necator, strain ZZH C-3 exhibited a lower H₂/CO₂ consumption ratio, superior substrate conversion efficiency, and high protein content. Overall, this study not only validated the potential of mangrove HOB for SCP production but also offers new insights for future metabolic engineering strategies designed to enhance CO₂-to-biomass conversion efficiency. Full article

Background: Isotomidae is one of the most common Collembola families, comprising 1484 species belonging to four subfamilies: Isotominae, Proisotominae, Anurophorinae, and Pachyotominae, while the subfamilial classification remains contentious and lack of molecular phylogenetic evidence. Methods: We sequenced and assembled the mitochondrial genomes (mitogenomes) of three species (Parisotoma sp., Folsomia sp. 1, and Folsomia sp. 2. Combining these with 10 mitogenomes available from GenBank, we reconstructed the phylogeny of Isotomidae based on a dataset of 13 species representing all four subfamilies. Results: These new mitogenomes, with lengths of 15,741 bp, 16,295 bp, and 16,765 bp, respectively, exhibit the typical metazoan gene set (13 PCGs, 22 tRNAs, 2 rRNAs) and show high structural conservation with other Collembola species. However, phylogenetic analyses based on concatenated protein-coding genes revealed significant incongruence with traditional classification. While Isotomidae was recovered as monophyletic, both Isotominae and Anurophorinae were recovered as paraphyletic. Specifically, Parisotoma sp. formed a distinct lineage closer to the derived subfamilies than to the core Isotominae, and the representative of Pachyotominae (Paranurophorus simplex) was recovered nested within Anurophorinae, suggesting potential subfamilial misclassification or paraphyly. Furthermore, Proisotoma minuta was identified as an independent sister lineage to the Anurophorinae + Pachyotominae clade. Conclusions: Our findings suggest that the current subfamily boundaries are not natural and that key diagnostic traits, such as furcal structure, likely reflect symplesiomorphies or various forms of homoplasy-including convergent evolution, parallelism, and evolutionary reversals—rather than unique synapomorphies defining monophyletic groups. This study provides essential genomic resources and highlights the need for an integrative taxonomic revision of Isotomidae that incorporates both molecular and morphological data, with particular emphasis on redefining subfamilies boundaries and reassessing diagnostic morphological traits. Full article

Background: Cleft palate (CP) is a prevalent craniofacial malformation, with the TGFβ pathway playing a critical role. Recent evidence links autophagy to regulating mouse embryonic palatal mesenchyme (MEPM) cells, but its interaction with TGFβ-activated phosphorylation cascades remains largely unknown. Here, we investigated the interplay between these pathways during palatogenesis. Methods: H&E and IHC analyses revealed increased expression of Beclin 1 and LC3 during the critical period of palatal shelf elevation and fusion (E13.5–E15.5). Bulk RNA sequencing (Bulk RNA-seq) further revealed enrichment of autophagy-related pathways and their interaction with TGFβ signaling. TMT-based phosphoproteomics was performed on TGFβ2-treated MEPM cells. Results: We identified 23,471 peptides and 3952 proteins, including 6339 phosphopeptides corresponding to 2195 phosphoproteins. Differential analysis found 477 phosphopeptides with increased abundance and 53 with decreased abundance, revealing the enrichment of seven serine (p-Ser) motifs (RxxS, SDxD, SDxE, SP, SxDE, SxEE, SxxxxD) and one threonine (p-Thr) motif (TP). Notably, kinase-substrate enrichment analysis identified CSNK2A as a previously unrecognized phosphorylation regulator, together with MAPKs and CDKs. Functional enrichment showed significant involvement of mTOR, MAPK, and autophagy/mitophagy pathways. Conclusions: Our findings revealed that TGFβ2 reshapes the MEPM phosphoproteome through Smad-independent pathway, expanding the palate-specific phospho-signaling atlas beyond the canonical Smad cascade. Full article

High-Mobility Group B (HMGB) proteins are conserved non-histone nuclear proteins involved in DNA replication, transcription, recombination, repair; plant growth and development; and stress responses. In this study, we identified nine ClHMGB genes in watermelon using genome-wide search. Phylogenetic and homology analyses classified them into four distinct classes. Synteny analysis revealed that ClHMGB genes share closer evolutionary relationships with dicots than with monocots. Tissue-specific expression profiling showed that eight ClHMGB members exhibit higher transcript levels in female and/or male flowers, suggesting that they play essential roles in floral organ development. Under drought, low-temperature, and salt stresses, ClHMGB members displayed distinct expression patterns. For instance, ClHMGB4 and ClHMGB8 were downregulated under drought and low-temperature stress but upregulated under salt stress, indicating potential functional specialization in response to different abiotic stresses. The highly virulent Fusarium oxysporum f. sp. niveum race 2 (Fon R2) induced the upregulation of more ClHMGB genes than the less virulent race 1 (Fon R1). Four members (ClHMGB1, 4, 6, and 7) were consistently upregulated by both races, suggesting that they may play fundamental roles in disease resistance. This study provides a foundation for further investigation into the roles of ClHMGB genes in growth, development, and stress responses of watermelon. Full article

Drought responses in poplar are genotype-dependent, yet standardized metrics for quantifying drought tolerance remain scarce. Here, we employed logistic modeling of relative electrolyte leakage (REC) for the first time in poplar to derive clone-specific semi-lethal polyethylene glycol (PEG) concentrations (LC₅₀), transforming a traditional descriptive assay into a quantitative, high-throughput drought-injury metric. Six elite Populus cultivars were exposed to increasing PEG concentrations, and their REC curves were fitted using a logistic function (R² = 0.885−0.981). The derived semi-lethal PEG concentration (LC₅₀) ranged from 7.99% in ‘PZ1’ (drought-sensitive, SS) to 13.44% in ‘YX2’ (drought-tolerant, ST), enabling clear classification. Under 10% PEG stress, ST maintained leaf water content (LWC) at 73%, while SS dropped to 63%. Malondialdehyde (MDA) content doubled in SS (44.7 nmol·g⁻¹ FW) but increased by only 25% in ST (33.5 nmol·g⁻¹ FW). Gas exchange analysis revealed that SS exhibited approximately twice the reduction in net photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs) compared to ST, with intercellular CO₂ accumulation (Ci) occurring only in SS—indicating both stomatal and non-stomatal limitations. Osmolyte profiling showed that SS accumulated large amounts of soluble sugars (Ss) (+128%) and proline (Pro) (+230%), whereas ST maintained stable soluble protein (Sp) levels and only moderately increased proline (+120%). Antioxidant capacity differed markedly: catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) activities increased by 5.6-, 1.8-, and 2.0-fold in ST, respectively, compared to 3.4-, 1.3-, and 1.7-fold in SS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of ten physiological traits explained 89% of the total variance (R²X = 0.954, Q² = 0.973), identifying POD, SOD, CAT, and Pro as the most discriminative variables (VIP > 1). This four-marker signature converts a conventional dose–response assay into a rapid, low-cost screening module that can be deployed in robotic phenotyping platforms. Specifically, the high-ranking genotype ‘YX2’ is recommended for immediate use in water-limited plantations and as a robust parent for next-generation dryland breeding programs. Full article

Background: The Tibetan Plateau, which is known for its high elevation and low oxygen levels, presents a challenging environment for its inhabitants. To adapt to these hypoxic conditions, species of Schizothoracine, a subfamily of Cyprinidae, have developed unique physiological mechanisms and functions. Transforming growth factor-β (TGF-β) is a multifunctional cytokine involved in the regulation of cell growth, differentiation, apoptosis, and the cellular immune response. However, its specific role in adaptation to hypoxia remains poorly understood. Methods: In this study, we aimed to characterize the TGF-β1 gene in Gymnocypris dobula (Gd) and Schizothorax prenanti (Sp) and to test whether TGF-β1 contributes to hypoxia adaptation in plateau Schizothoracine fish. The predicted protein for Gd-TGF-β1 contains several primary domains, including cwf21 (cdc5 protein 21), GYF (Glycine-Tyrosine-Phenylalanine), FN1 (Fibronectin 1), a conservative domain, and a signal peptide. Results: The results of tissue distribution revealed that the mRNA level of TGF-β1 in brain, heart, muscle, skin, gills, and spleen—which are key tissues involved in oxygen sensing, transport, and physiological adaptation to hypoxic environments—was significantly lower in G. dobula than that in S. prenanti. Western blotting analysis revealed that the expression of activated TGF-β1 in G. dobula was significantly higher than that in S. prenanti. To investigate whether TGF-β1 in G. dobula possesses hypoxic adaptive features, Gd-TGF-β1 and Sp-TGF-β1 were cloned into an expression vector and transfected into 293-T cells, which are widely used due to their ease of culture, high transfectability, and well-characterized properties. We found that the survival rate of cells transfected with Gd-TGF-β1 was significantly higher than that of cells transfected with Sp-TGF-β1 after hypoxia treatment. Conclusions: These findings suggest that G. dobula may promote hypoxic adaptation through the activation and increased expression of TGF-β1. Changes in TGF-β1 expression may play a role in the adaptation of G. dobula to hypoxic conditions. Full article

Background: Pediatric sepsis is a life-threatening disease that is associated with the progression of acute lymphoblastic leukemia (ALL) and the recurrence of B-cell ALL (B-ALL). Although previous studies have reported a partial association between sepsis and ALL, there is limited research on the shared genes between pediatric sepsis and relapsed B-ALL. This study aims to further elucidate the more comprehensive and novel common genetic factors and molecular pathways between the two diseases. Methods: Gene expression datasets pertaining to pediatric sepsis (GSE13904, GSE80496) and relapsed B-ALL (GSE3910, GSE28460) were retrieved from the Gene Expression Omnibus database for this retrospective analysis. The initial analysis identified differentially expressed genes common to both pediatric sepsis and relapsed B-ALL. Subsequent investigations employed three complementary approaches: protein–protein interaction networks, molecular complex detection (MCODE) clustering functions, and support vector machine recursive feature elimination model to separately identify the diagnostic biomarkers for each condition. Importantly, key common genes were identified by overlapping the diagnostic genes for pediatric sepsis and relapsed B-ALL. Further characterization involved comprehensive functional analysis through the Metascape platform, construction of transcription factor (TF)-mRNA-microRNA (miRNA) networks, drug prediction, and molecular docking to explore their biological significance and potential therapeutic targets. Results: Comparative analysis of pediatric sepsis-related and relapsed B-ALL-related datasets revealed two shared genetic markers, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9), exhibiting diagnostic significance and consistent upregulation in both disease groups. Transcriptional regulatory network analysis identified specificity protein 1 (SP1) as the principal transcription factor capable of coregulating LTF and MMP9 expression. In addition, molecular docking demonstrated high-affinity interactions between curcumin and MMP9 (−7.18 kcal/mol) as well as reserpine and LTF (−5.4 kcal/mol), suggesting their potential therapeutic utility for clinical evaluation. Conclusions: These findings elucidate the molecular pathogenesis involving LTF and MMP9 in pediatric sepsis and relapsed B-ALL, providing novel insights for clinical diagnosis and therapeutic development. Full article

Hydrogen sulfide (H₂S) exerts regulatory functions in kidney diseases. However, its protective role against kidney stone formation remains unclear. Here, we demonstrate that hyperoxaluria or oxalate exposure impairs H₂S formation, leading to tubular injury and calcium oxalate (CaOx) crystal deposition in both in vivo and in vitro models. In male rats fed 5% hydroxy-L-proline (HP), time-dependent increases in urinary supersaturation, tubular damage, and renal CaOx deposition were observed compared to controls. These changes were associated with the decreased expression of H₂S-producing enzymes and elevated urinary secretion of osteopontin (OPN) and Tamm–Horsfall protein (THP). Notably, the protein level and activity of specificity protein 1 (Sp1), a transcription factor regulating these enzymes, were markedly decreased in HP-treated kidneys. Chronic supplementation with the H₂S donor GYY4137 (GYY) significantly attenuated HP-induced tubular injury and CaOx deposition by reducing OPN and THP secretion. Consistent with in vivo results, H₂S donors mitigated oxalate-induced tubular cell damage and CaOx formation in MDCK cells. Mechanistically, oxalate activated cyclic AMP/protein kinase A (PKA) signaling, which promoted OPN and THP secretion; these effects were eradicated by the PKA inhibitor H89 or GYY. These findings indicate that hyperoxaluria impairs Sp1 transcriptional activity, resulting in H₂S deficiency and compromised anticrystallization defense in oxalate-induced tubulopathy. Full article

Peptaibols are linear fungal peptides featuring α,α-dialkylated amino acids (e.g., α-aminoisobutyric acid (Aib), isovaline (Iva)) and characteristic C-terminal alcohol groups. Despite their promising antibacterial and antiplasmodial activities, detailed biosynthetic studies remain limited. A genome-guided study of the fungus Trichodema sp. SK1-7, isolated from decaying wood, revealed the production of previously described trichorozin IV (1), along with novel SF4-type peptaibol 2 (trichorozin V). The structures of these compounds were elucidated through MS analysis, NMR study and advanced Marfey’s method. The genome of Trichoderma sp. SK1-7 harbors two PKS-NRPS hybrid gene clusters containing 14 and 18 adenylation domains. Analysis of the modular architecture suggested that trichorozins are synthesized by a 14-module protein via a module skipping mechanism. Genome mining revealed several types of short peptaibol synthase architectures (10–14 adenylation domains) across various Trichoderma species, accompanied by similar long peptaibol synthases. Furthermore, putative Aib/Iva biosynthesis machinery in Trichoderma was identified, showing specific architectures potentially involved in regulating peptaibol biosynthesis. Feeding experiments demonstrated that peptaibol production depends on the ratio of Iva/Aib. The isolated compounds exhibited moderate antibacterial and cytotoxic activities along with a synergistic effect when combined with membrane-targeting antibiotics. Our findings suggest that genome-guided approaches hold promise for further development of peptabiotics with a wide range of applications, including antibiotic adjuvants. Full article