Search Results (420)

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes. Full article

Frequent outbreaks of bacterial and fungal diseases in aquaculture cause severe economic losses, making biological control using probiotics a crucial strategy. Bacillus velezensis synthesizes diverse antimicrobial secondary metabolites; however, its biocontrol potential is tightly regulated by environmental signals such as cultivation time. In this study, we investigated the effect of growing time on the antifungal activity of B. velezensis GHZJ-1, isolated from an aquatic environment. It was found that GHZJ-1 shows obvious antifungal activity against the aquatic pathogen Metschnikowia bicuspidata upon 48 h growth but no such activity for 24 h via the agar-diffusion method. We further compared the transcriptomes of GHZJ-1 cells collected at 24 h and 48 h through RNA-Seq. Our results revealed that compared with 24 h, 1821 genes were differentially expressed at 48 h, with 903 upregulated and 918 downregulated. Downregulated genes were enriched in primary metabolic pathways (e.g., ribosome assembly and carbon metabolism), whereas upregulated genes were enriched in secondary metabolite biosynthesis and transmembrane transport. Importantly, 35 upregulated genes directly associated with antimicrobial activity were identified, notably including the ones encoding core elements of a large polyketide synthase (e.g., pksN, log₂FC = 2.24), the petrobactin siderophore system (highest log₂FC = 3.39), and various antimicrobial peptide export systems. Furthermore, the degU gene was activated at 48 h. These data suggest that facing continuously increased environmental stress over time, GHZJ-1 undergoes global transcriptional reprogramming and resource reallocation, downregulating basal metabolism to construct a synergistic antagonistic system coupling chemical defense with nutritional competition. This study elucidates the time-dependent mechanism for antifungal activity in GHZJ-1, providing a molecular theoretical basis for its green biocontrol application in aquaculture diseases caused by fungi. Full article

Antimicrobial peptides (AMPs) occur naturally in living organisms and play an essential role in defense against pathogens. Consequently, these peptides are significant in public health research as alternatives in addressing microbial resistance. Here, we present the proteomic profile of Cryptococcus neoformans treated with RcAlb-PepII, an AMP derived from the 2S albumin of Ricinus communis seed cake. This research is noteworthy, as C. neoformans is an emerging fungal pathogen classified by the World Health Organization (WHO) as a critical threat. Proteomic analysis revealed depletion of proteins involved in DNA and RNA metabolism, reduced protein biosynthesis, and mitochondrial damage-associated proteins in C. neoformans following RcAlb-PepII treatment. These findings advance the understanding of the therapeutic profile of AMPs and underscore their importance in combating critical pathogens. Full article

The SUN family protein MoSun4 in Magnaporthe oryzae has been previously implicated in mitophagy and has potential as a target for reducing rice blast, but its role as a secreted protein remains poorly understood. In this study, signal peptide prediction and yeast secretion assays confirmed MoSun4 signal peptide function, and co-localization revealed the localization of the extra-invasive hyphal membrane (EIHM)-associated apoplastic compartment or matrix, establishing MoSun4 as a secreted protein. In addition, deletion of the MoSUN4 gene reduced the hyphal growth, conidiation and virulence of M. oryzae. We further showed that MoSun4 is involved in regulating the expression of virulence-related genes, including multiple genes involved in cell wall degradation (eglC, eglD), secondary metabolism (gliK), and melanin biosynthesis (SDH1, BUF1, Cmr1, ALB1). Collectively, our study reveals that MoSun4 is a secreted protein that contributes to pathogenicity and is associated with altered expression of virulence-related genes, providing new insights into the functions of SUN family proteins. Full article

Yeast hydrolysate (YH) is a yeast-derived functional feed ingredient containing bioactive peptides, amino acids, nucleotides, β-glucans, and mannan oligosaccharides, which may exert prebiotic-like effects by regulating nutrient metabolism, host health, and intestinal microbial homeostasis. However, its effects on lactating Dezhou jennies remain largely unclear. This study investigated the effects of dietary YH supplementation on body weight change, serum biochemical parameters, serum metabolomic profiles, and fecal microbiota composition in lactating Dezhou jennies. Sixteen healthy lactating Dezhou jennies were randomly assigned to a control group fed a basal diet (MCON, n = 8) or a YH supplementation group fed the basal diet supplemented with YH (MYE, n = 8) for 60 days. Compared with the MCON group, the MYE group showed numerically higher final body weight and body weight change. Serum biochemical analysis showed that YH supplementation significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and increased triglyceride (TG) concentrations, while all measured biochemical parameters remained within physiological reference ranges. Serum metabolomic profiling identified 193 differential metabolites between the two groups, including 55 upregulated and 138 downregulated metabolites in the MYE group. These metabolites were mainly associated with amino acid metabolism, lipid metabolism, bile acid metabolism, steroid hormone biosynthesis, mineral absorption, ABC transporters, and protein digestion and absorption, indicating that YH supplementation reshaped nutrient-related metabolic pathways in lactating Dezhou jennies. Fecal microbiota analysis showed no significant changes in α-diversity or overall community structure; however, the MYE group displayed numerically higher microbial richness indices, more unique ASVs and genera, a lower relative abundance of Bacteroidota, and a higher relative abundance of Bacillota. LEfSe analysis further revealed enrichment of specific bacterial taxa in the MYE group, including Christensenellaceae_R-7_group, Anaerovorax, and UCG-related taxa. Collectively, these preliminary findings suggest that dietary YH supplementation may alter selected serum biochemical indices and circulating metabolites and may selectively affect the relative abundance of certain fecal bacterial taxa in lactating Dezhou jennies. However, given the limited sample size, these results should be interpreted cautiously, and larger-scale studies are needed to confirm their reproducibility and practical significance. Full article

Background/Objectives: Clematis huchouensis Tamura, a genuine medicinal herb endemic to Huzhou, Zhejiang Province. However, its secondary metabolic profile and organ-specific distribution of bioactive constituents remain largely uncharacterized. This study aims to systematically characterize the metabolic profile of its roots, stems, and leaves, and to elucidate organ-specific accumulation patterns of pharmacologically relevant constituents, thereby providing a scientific basis for resource evaluation and quality control of this regional germplasm. Methods: A widely targeted metabolomics approach was employed to profile metabolites in the roots, stems, and leaves of C. huchouensis. Comprehensive annotation and relative quantification were performed using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) combined with database matching. Cluster analysis and pathway enrichment were conducted to compare metabolic profiles across organs. Results: A total of 1561 metabolites were identified, exhibiting distinct organ-specific accumulation patterns. Flavonoids, alkaloids, and most phenolic acids were predominantly enriched in the aerial parts, whereas the roots accumulated high levels of glutathione and its related peptides, reflecting their significant antioxidant activity. Amino acids displayed complementary tissue-specific distribution, with peptides enriched in leaves and sulfur-containing amino acids such as L-methionine in stems. Organ-specific metabolic differences were significantly associated with pathways including flavonoid biosynthesis and linoleic acid metabolism. Notably, numerous pharmacologically active compounds, such as hispidulin, diosmetin, trigonelline, colchicoside, and oleanolic acid-3-O-xylosyl(1→3)glucuronide—exhibited marked tissue-selective accumulation. Conclusions: This first metabolomic study of C. huchouensis reveals organ-specific accumulation of bioactive compounds, providing a metabolic foundation for its quality control and rational utilization. Full article

Trigonelline is a bioactive pyridine alkaloid in Trigonella foenum-graecum, which is a legume species, and is known for its hypoglycemic and hypolipidemic activities. Phytosulfokine-δ (PSK-δ), a recently identified legume-specific phytosulfokine peptide, has been implicated in the regulation of nodulation and root development. However, whether PSK-δ participates in the regulation of secondary metabolite biosynthesis remains unclear. In this study, exogenous PSK-δ treatment significantly promoted trigonelline accumulation in T. foenum-graecum seedlings, leading to a 93% increase in trigonelline content after 5 days relative to the scrambled-pentapeptide-treated control, whereas a slight downward trend was observed at 15 days. Comparative transcriptomic analyses between PSK-δ-treated seedlings and the corresponding controls at 5 and 15 days identified 15 candidate genes associated with trigonelline biosynthesis and PSK signaling, whose expression patterns were consistent with trigonelline accumulation dynamics. Co-expression network analysis between these 15 candidate genes and 831 transcription factor-encoding genes identified candidate transcription factors potentially involved in the coordinated regulation of trigonelline biosynthesis and PSK signaling. These findings suggest that PSK-δ may serve as a potential peptide-based biostimulant for regulating alkaloid accumulation in medicinal legume cultivation and provide insights into peptide hormone-mediated regulation of plant metabolism. Full article

Thanatin is a small cationic antimicrobial peptide with broad-spectrum antibacterial activity, considered a promising candidate to combat the global antibiotic resistance crisis. Microbial biosynthesis represents an attractive strategy for sustainable production of antimicrobial peptides. In this study, we constructed a heterologous expression system for thanatin in Saccharomyces cerevisiae CENPK2 using both PiggyBac (PB) and Ty2 retrotransposon systems, demonstrating the utility of yeast as a host for peptide production and transposon-based genetic engineering. By designing transposon-based expression plasmids incorporating the CL1 selection tag, we achieved efficient expression of thanatin. The expression of thanatin-derived peptides was confirmed by Tris-tricine-SDS-PAGE and liquid chromatography-mass spectrometry (LC-MS). In vitro antibacterial assays demonstrated that the fermentation supernatant of engineered yeast significantly inhibited the growth of Escherichia coli O157: H7, Salmonella typhimurium, Aeromonas veronii (JL-2), and Acinetobacter baumannii. Notably, strains harboring both PB and Ty2 systems exhibited stronger antibacterial activity than those with a single system. Scanning electron microscopy further revealed that thanatin caused damage to bacterial cell membranes and led to cell lysis. Hemolysis tests proved that the physiological saline-replaced fermentation supernatant possessed low hemolytic activity. This study successfully established a transposon-based platform for the heterologous expression of thanatin. Full article

Rhodococcus species display remarkable metabolic versatility and adaptation to extreme environments, yet their antimicrobial potential remains largely unexplored, particularly in strains representing undescribed genomic lineages. This study investigated whether the genome of Rhodococcus sp. GB-02, a strain isolated from Antarctic soil, encodes antimicrobial peptides with demonstrable activity against clinically relevant pathogens. Hybrid genome assembly revealed a 6.58 Mb high-quality draft genome belonging to a previously undescribed genomic lineage within the genus Rhodococcus, based on average nucleotide identity and digital DNA–DNA hybridization analyses. Genome mining identified 20 biosynthetic gene clusters, predominantly non-ribosomal peptide synthetases, several of which showed low or no similarity to known pathways. Eight putative antimicrobial peptides (AMPs) were computationally predicted; among these, three lacked detectable homology to sequences in current databases, and experimental validation of one predicted peptide, designated Peptide 5764, demonstrated antibacterial activity at high micromolar concentrations against Gram-positive and Gram-negative pathogens and concentration-dependent inhibition of biofilm formation, particularly in Pseudomonas aeruginosa. However, Peptide 5764 exhibited considerable hemolytic activity at antibacterial concentrations, indicating that optimization for membrane selectivity will be required before therapeutic application. These findings establish Rhodococcus sp. GB-02 as an underexplored Antarctic lineage with a diverse biosynthetic repertoire and provide proof-of-concept that genome-guided AMP prediction can identify experimentally active peptide scaffolds from this lineage. Full article

Background: Lung infections represent a major cause of morbidity and mortality in patients with cystic fibrosis (CF) and are predominantly associated with chronic infection by Pseudomonas aeruginosa. The clinical management of CF lung disease is increasingly compromised by the emergence of multidrug-resistant strains, biofilm formation, and the expression of multiple virulence determinants. Antimicrobial peptides (AMPs), evolutionarily conserved effectors of innate immunity, have emerged as promising therapeutic candidates due to their ability to exert both bactericidal and anti-virulence activities. In this study, we investigated the antimicrobial and mechanistic effects of Ranalexin-1G, an AMP derived from the skin secretion of Rana grylio, against P. aeruginosa, for which its antibacterial activity has not previously been reported in the literature. Methods: Antibacterial activity was determined against the reference strain and three clinical isolates of P. aeruginosa by broth microdilution assays, time-kill kinetics and anti-biofilm assays, while peptide-mediated modulation of virulence was evaluated through transcriptional analysis of key virulence-associated genes by RT-PCR. The impact of Ranalexin-1G on host–pathogen interactions was further assessed using bacterial invasion assays in human bronchial epithelial cells (BEAS-2B). Results: Ranalexin-1G exerted a rapid bactericidal effect within 6 h at non-cytotoxic concentrations and displayed modest anti-biofilm effects, with greater efficacy in inhibiting biofilm formation. Mechanistically, peptide treatment resulted in a reduction in the expression of selected genes involved in biofilm formation and virulence, including those associated with alginate biosynthesis and type III secretion system-mediated cytotoxicity. Consistently, Ranalexin-1G markedly impaired bacterial invasion of epithelial cells, indicating interference with early host–pathogen interaction processes. Notably, the peptide displayed robust antimicrobial activity against multidrug-resistant P. aeruginosa clinical isolates from CF patients. Conclusions: Collectively, these findings suggest that Ranalexin-1G acts through a dual mechanism involving direct bactericidal activity and modulation of selected virulence pathways, supporting further investigation of its potential as an anti-virulence and host-directed approach for the treatment of chronic P. aeruginosa infections in cystic fibrosis. Full article

Perilla seed extract (PSE), a natural resource rich in α-linolenic acid and flavonoids, represents a promising dietary strategy to sustainably optimize rumen fermentation and improve the nutritional profile of ruminant meat. This study evaluated the effects of dietary PSE supplementation on rumen fermentation, microbiome–metabolome profiles, and subsequent meat quality in Tan lambs. Sixty 3-month-old male Tan lambs were randomly assigned to four dietary treatments (n = 15 per treatment) containing 0% (CON), 0.01% (LPSE), 0.03% (MPSE), or 0.05% (HPSE) PSE on a dry matter (DM) basis. In the rumen, the 0.03% PSE inclusion increased the propionate proportion from 20.50% to 23.80% (P-linear = 0.004) and carboxymethyl cellulase activity from 12.45 to 14.85 U/mL (P-linear = 0.007; P-quadratic = 0.045). Exploratory metagenomics showed that 0.03% PSE enriched Prevotella (18.67% to 21.06%) and Ruminococcus_E (1.20% to 2.13%), while decreasing the biohydrogenating genus Butyrivibrio compared with CON (LDA > 2, p < 0.05). These microbial shifts were accompanied by the accumulation of beneficial metabolites (e.g., small peptides and itaconic acid) and up-regulation of the pantothenate and CoA biosynthesis pathway. Consequently, the 0.03% PSE diet optimized meat quality, decreasing shear force by 12.7% (from 45.65 to 39.85 N; P-linear = 0.005, P-quadratic = 0.018) and drip loss (from 4.82% to 3.85%; P-linear = 0.022, P-quadratic = 0.015), while increasing redness (P-linear = 0.012, P-quadratic = 0.045). Furthermore, it increased meat C18:3n-3 (from 0.62% to 0.91%) and total n-3 PUFA (from 1.12% to 1.52%), while decreasing the n-6/n-3 ratio from 6.76 to 5.13 (P-linear ≤ 0.005 for all). Flavor amino acids also increased (P-linear = 0.008). These findings suggest that 0.03% PSE supplementation potentially improves lamb meat quality by favorably modulating rumen fermentation and microbe-metabolite interactions, highlighting its promise as a natural feed additive, though further validation is warranted. Full article

Water-soluble blue microbial pigments with antioxidant activity remain rare, and their host-level protective mechanisms are poorly understood. Here, we identified the genetic basis of blue pigment biosynthesis in the glacier-derived strain Arthrobacter antioxidans QL17. Heavy-ion mutagenesis yielded a hyperpigmented mutant (M157) and a pigment-deficient mutant (M186), and pigment yield was positively associated with hydrogen peroxide (H₂O₂) tolerance. Genome mining identified MWM45_RS16760 as the sole core biosynthetic gene in a candidate nonribosomal peptide synthetase (NRPS)-like cluster. The encoded protein displayed an adenylation–peptidyl carrier protein–thioesterase (A-PCP-TE) architecture with a predicted L-glutamine-specific A domain, and its transcript abundance paralleled pigment production across the three strains. Phylogenetic analysis placed MWM45_RS16760 in a distinct actinomycete-associated indigoidine-like lineage separated from the characterized BpsA and IndC branches. Heterologous expression in Escherichia coli reconstructed a blue-pigment-producing phenotype, increased H₂O₂ tolerance, and was accompanied by enhanced extracellular DPPH and ABTS radical-scavenging activities in the culture supernatant. Comparative transcriptomics further revealed coordinated activation of oxidative-stress and proteostasis responses alongside repression of tryptophan biosynthesis and flagellar assembly. These findings identify MWM45_RS16760 as a candidate indigoidine-like NRPS associated with blue pigment biosynthesis and oxidative-stress resistance, with heterologous expression linked to enhanced radical scavenging and coordinated transcriptional reprogramming, expanding the phylogenetic and functional diversity of indigoidine-like systems. Full article

Pancreatic β-cells maintain glucose homeostasis through tightly regulated insulin biosynthesis, storage, and secretion. To prevent pathological accumulation of excess or aging secretory granules (SGs), β-cells use crinophagy, a selective lysosomal degradation pathway in which mature insulin-containing granules fuse directly with lysosomes to form hybrid organelles termed crinosomes. Crinophagy was historically considered a simple mechanism for discarding obsolete, aged SGs. The acidic, protease-rich environment of crinosomes is proposed to generate unconventional insulin-derived epitopes through cathepsin-mediated proteolysis and transpeptidation reactions. These cryptic epitopes, which include hybrid insulin peptides (HIPs) resulting from the covalent fusion of insulin fragments with peptides from co-resident granule proteins, are largely absent from the thymic epitope repertoire. This creates a “peripheral–thymic mismatch” that allows autoreactive CD4+ T cells to escape central tolerance, ultimately driving β-cell destruction in type 1 diabetes (T1D). Recent studies demonstrate that pharmacological or genetic inhibition of crinophagy reduces crinosome abundance, narrows the pathogenic epitope repertoire, and delays the onset of diabetes in preclinical models. In type 2 diabetes (T2D), a related pathway termed stress-induced nascent granule degradation (SINGD) diverts newly synthesized insulin granules to lysosomes under glucolipotoxic conditions, contributing to insulin depletion and progressive β-cell failure. This review summarizes the current understanding of the molecular mechanisms behind crinophagy. It discusses its two main functions: maintaining physiological quality control and generating pathological antigens. Additionally, the review explores how crinophagy interacts with other cellular stress pathways and highlights new therapeutic strategies aimed at targeting this process to protect pancreatic β-cell function and potentially prevent or delay diabetes. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging global health concern due to population mobility. Although benznidazole and nifurtimox remain the only approved antiparasitic drugs, their limited efficacy in chronic infection, prolonged treatment regimens, frequent adverse effects, and variable activity across parasite strains highlight the need for new therapeutic strategies. In addition, the pathogenesis of chronic Chagas disease is driven not only by parasite persistence but also by immune-mediated tissue damage, particularly in chronic Chagas cardiomyopathy. In this review, we examine emerging therapeutic approaches that extend beyond conventional trypanocidal chemotherapy, with emphasis on natural products, antimicrobial peptides, and cell-based immunomodulatory strategies. Plant compounds and essential oils have shown antiparasitic activity through mechanisms including oxidative stress induction, membrane disruption, interference with sterol biosynthesis, and mitochondrial dysfunction, while some extracts also modulate host immune responses. Antimicrobial peptides display dual potential by directly damaging parasite membranes and organelles or by reshaping infection-associated inflammatory responses. In parallel, cell-based therapies such as mesenchymal stromal cells, tolerogenic dendritic cells, and bone marrow-derived cells have demonstrated promising cardioprotective and immunoregulatory effects in experimental chronic Chagas disease. Collectively, these approaches support a multitarget therapeutic framework in which parasite-directed and host-directed interventions may complement each other. Further mechanistic studies, standardization, and translational validation will be essential to advance these candidates toward clinically useful therapies for Chagas disease. Full article

The growing concern over antimicrobial resistance and the increasing demand for safer and more sustainable antimicrobial strategies have driven extensive research into peptide-based natural antimicrobials. This review focuses specifically on antimicrobial peptides (AMPs), bacteriocins and mycocins as peptide- or proteinaceous antimicrobial compounds with potential applications as active ingredients, biopreservatives and antimicrobial tools. These compounds exhibit activity against spoilage and pathogenic microorganisms and are increasingly being explored in food safety, agriculture, cosmetics, animal health and human healthcare. AMPs, bacteriocins and mycocins act through diverse and sometimes overlapping mechanisms, including membrane disruption, pore formation, inhibition of cell wall biosynthesis, interference with intracellular targets, induction of oxidative stress and modulation of host or microbial responses. These mechanisms support their potential use in food biopreservation, crop protection, biofungicide and biopesticide development, topical antimicrobial formulations, cosmetic preservation, antibiofilm strategies and adjunctive therapeutic approaches. Recent advances in encapsulation, peptide engineering, recombinant production, nanodelivery and combination strategies with conventional antibiotics, hurdle technologies or other natural antimicrobials have improved the stability, bioavailability and antimicrobial efficacy of these compounds in experimental systems. However, broader translation remains limited by several major challenges. These include proteolytic degradation, reduced stability in complex matrices, context-dependent antimicrobial activity, possible toxicity, resistance development, high production and purification costs, formulation difficulties, scale-up limitations and regulatory constraints. Further validation is also needed regarding safety, microbiome impact, environmental fate and performance under realistic food-preservation, agricultural, cosmetic and clinical conditions. This review summarises and compares the diversity, mechanisms, applications and translational challenges of AMPs, bacteriocins and mycocins across food safety, sustainable agriculture, cosmetics, animal health and healthcare. It also discusses the main challenges that must be addressed before broader translation, including resistance risk, stability, formulation, scale-up, safety assessment and regulatory approval. Full article