Natural polyketide enterocin inhibits ASGR1 to enhance cholesterol efflux and regulate hepatic lipid metabolism.

Sustainable valorization of rapeseed meal to bioactive and nutritional products via solid-state fermentation with protease-enhanced Streptomyces sp. SCUT-3

Streptomyces species are valuable allies in sustainable agriculture due to their ability to produce a diverse range of bioactive metabolites. This current study aimed to investigate the antioxidant, plant growth-promoting, and biocontrol potential of Streptomyces sp. SP5 against Fusarium wilt in Capsicum annuum. SP5 acetone precipitates and Et₂O extract exhibited strong dose-dependent antioxidant activity in multiple radical scavenging assays. In vitro seed bioassays with Vigna radiata revealed that SP5-derived indole-3-acetic acid markedly enhanced germination and early seedling growth, which was further supported by improved vegetative growth in pot experiments with Solanum lycopersicum. Furthermore, SP5 displayed remarkable biocontrol efficacy against Fusarium solani in Capsicum annuum. Under in vivo conditions, SP5 significantly reducing wilt incidence while simultaneously improving plant vigor and agronomic traits. SP5 treatments also enhanced photosynthetic pigment levels and stimulated the accumulation of phenolic and flavonoid compounds, indicating activation of plant defense responses under both stressed and non-stressed conditions. Overall, Streptomyces sp. SP5 functions as a multifunctional strain with combined antioxidant, growth-promoting, and biocontrol properties, highlighting its potential as an eco-friendly strategy for improving crop productivity and disease management.

Thioamides constitute an important class of pharmaceutically active natural products, yet their discovery and development are limited. A targeted metabologenomic method is developed to logically and efficiently discover thioamide compounds in bacteria. To this end, two strains were identified to possess genetic capacity for biosynthesizing thioamides from the bacterial genomic DNA library (1,192 strains) using the polymerase chain reaction to target the TfuA-encoding gene, a genomic hallmark of thioamide biosynthesis. Mass spectrometric isotopic patterns of sulfur-bearing compounds serve as metabolomic hallmarks to detect thioamide production from the extracts of the selected strains without chromatography. Applying this metabologenomic targeting approach, two new thioamides, thiogochangamides A and B, belonging to the thioviridamide family whose stereochemistry has remained unresolved for two decades, were discovered in Streptomyces sp. Their absolute configurations were fully assigned through chemical derivatizations, including the advanced Marfey method, Mosher method, partial hydrolysis, synthesis of an unusual amino acid, and desulfurization, combined with computational methods. Thiogochangamide B exhibits potent inhibitory activity against gemcitabine-resistant pancreatic cancer cells both in vitro and in vivo. Mechanistically, thiogochangamide B effectively downregulates Wnt/β-catenin signaling, thereby suppressing the metastatic potential of drug-resistant cancer cells. This study provides a new therapeutic strategy for overcoming recalcitrant drug-resistant pancreatic cancer.

Actinobacteria produce a plethora of bioactive molecules, yet research on these bacteria in the Pacific Island nations remains scarce. Previously, we isolated 16 actinomycete strains from Fijian hard corals, with varying degrees of antimicrobial activity against common pathogenic strains. The present study aims to identify these bioactive actinomycete isolates using 16S ribosomal RNA (16S rRNA) gene sequencing and phylogenetic analysis. The 16S rRNA gene characterization of the bioactive isolates predominantly revealed members of the genus Streptomyces, alongside three rare actinomycete genera: Micromonospora, Prauserella, and Kocuria. Additionally, antiSMASH analysis of the closest phylogenetic relatives of these cultured actinobacteria with notable antimicrobial activity revealed a strong potential for antibiotic biosynthesis. Overall, these findings suggest that Fijian hard corals represent a promising reservoir of bioactive actinobacteria for the discovery of antimicrobial compounds, particularly Streptomyces spp.

Genome-guided mining of marine Streptomyces sp. GCU-142 led to the identification of three unprecedented sugar-bearing anthracycline glycosides, igidamycins A-C (1-3). The structures of 1-3 were assigned by spectroscopic analysis including NMR, HR-MS, and UV spectroscopy. Their configurations were determined by ROESY NMR data, the modified Mosher's method, l-cysteine methyl ester derivatization, and TD-DFT ECD calculations. Bioinformatic analysis suggested a plausible biosynthetic pathway of igidamycins, integrating type II polyketide assembly, extensive sugar tailoring, and late-stage nitration. Notably, igidamycin A (1), bearing a nitro group at C-6, exhibited potent antibacterial activity against various Gram-positive pathogens. In contrast, the non-nitrated congeners (2 and 3) were inactive, highlighting a key role of the nitro functionality in its antibacterial potency.

Ansamycins constitute a structurally distinctive class of macrolactams characterized by the 3-amino-5-hydroxybenzoic acid (AHBA) starter unit and a broad spectrum of pharmacological activities. Genome mining of the rhizosphere-derived Streptomyces sp. LR417 revealed a cryptic ansamycin biosynthetic gene cluster (pas) that remained transcriptionally silent under standard laboratory culture conditions. A combinatorial activation strategy, integrating the constitutive overexpression of pathway-specific positive regulators with AHBA precursor supplementation, successfully unlocked the biosynthetic potential of this cluster, affording 11 new pentaketide ansamycins, pannansamycins A-K (1-11). Compound 1 displayed potent radical-scavenging activity, while compounds 2 and 3 displayed moderate radical-scavenging and lipoxygenase inhibitory activities. These findings expand the structural diversity of the ansamycin family and provide new scaffolds with antioxidant potential worthy of further investigation.

Phenazinoates A-E (1-5), comprising five pairs of methyl saphenate conjugates with genistein, o-aminophenol, p-acetaminophenol and glycerol, were isolated from the fermentation broth of mangrove soil-derived Streptomyces sp. OUCMDZ-4923. Their structures were determined through comprehensive one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, coupled with high-resolution electrospray ionization mass spectrometry. The absolute configurations of each isomer were established by comparing experimental electronic circular dichroism spectra with calculated counterparts. Based on the biosynthetic pathway analysis, compounds 1‒3 were semi-synthesized from the reactions of methyl (R)-saphenate with genistein, o-aminophenol, and o-formamidophenol, utilizing microwave-assisted solid acid catalysis. The compounds were resolved as enantiomerically pure forms and subsequently tested for antibacterial efficacy against six pathogenic bacteria. Phenazinoates A (1) and B (2) demonstrated bioactivity against four Gram-positive bacterial strains, with minimum inhibitory concentration values ranging from 0.78 to 3.13μg/mL.

Three new naphthomycin derivatives were isolated and identified from Streptomyces sp. HKIB0008, and were designated as naphthomycin R (1), naphthomycin S (2), and naphthomycin T (3). Their structures were elucidated using a combination of spectroscopic techniques, including high-resolution mass spectrometry, and NMR. The naphthoquinone core of 1 underwent carbon-carbon bond cleavage, resulting in a novel structural feature, and a corresponding Baeyer-Villiger oxidation mechanism was proposed. Compounds 2 and 3 possess a complex side chain when compared to known cystine modification on the naphthalenoid core as in the case of naphthomycins I and J. In addition, the minimum inhibitory concentration (MIC) assays for these compounds were conducted.

Chemical investigation of an Australian pasture soil-derived Actinomadura sp. prioritized for anthelmintic properties, led to the isolation and characterization of four new triamide-hydroxamates, goondastatins A1-D1 (1-4), with structures assigned on the basis of detailed spectroscopic analysis and chemical degradations/derivatization (Marfey's and Mosher analyses). The corresponding oxazoles, goondastatins A2-D2 (1a-4a) were also detected and tentatively identified. An expanded investigation of four additional Australian pasture soil-derived Streptomyces spp., also prioritized for anthelmintic properties, led to the discovery of goondastatin E2 (5) as a hydrolysis handling artifact of the known cometabolite kasichelin C (5a), two new piperazines, goondazines A (6) and B (9), and the known piperazines XR334 (7) and piperafizine A (8) with structures assigned by detailed spectroscopic and chemical analysis. While much of the anthelmintic properties of the pasture soil actinomycete could be attributed to known natural product classes (e.g., maduramicins and piericidins), goondastatin E1 (5) exhibited moderate and selective inhibition of dog heartworm Dirofilaria immitis microfilariae motility (EC50 = 4.1 μg/mL). Goondazine A (6), in contrast, exhibited moderate inhibition of livestock (ruminant) gastrointestinal nematode Hemonchus contortus L1-L3 larval development (EC50 = 1.2 μg/mL) and weak inhibition of D. immitis microfilariae motility (EC50 = 15 μg/mL).

Defined microbial consortium with bioremediation potential: atrazine removal, phytotoxicity, and detection of genes involved in herbicide catabolism.

Two new naphthoquinone-naphthalene hybrid dimers featuring a complex polycyclic fused skeleton, named chimedermycins O (1) and P (2), were isolated from the marine-derived Streptomyces sp. OUCMDZ-4982. Their structures, including the absolute configurations, were established by spectroscopic methods and quantum chemical calculations. These compounds are formed through the coupling of medermycin, a major metabolite produced by the same strain, with naphthalene-1,8-diol derivatives. Both compounds exhibited significant cytotoxicity against two human cancer cell lines (MDA-MB-231 and MGC-803) with IC50 values ranging from 2.30 to 9.78 µM.

Marine Streptomyces-derived 2,4-di-tert-butylphenol enhances autophagy to eliminate mycobacteria in human macrophages.

A new microbial secondary metabolite, paulobutalipin (1), was isolated and characterized from the culture of a mountain soil-derived Streptomyces strain. The structure of paulobutalipin (1) was elucidated through a combined analysis of spectroscopic data, single-crystal X-ray diffraction, chemical modifications including application of the modified Mosher's method, and electronic circular dichroism calculations. In an in vitro hepatocellular steatosis model induced by palmitic and oleic acids, paulobutalipin (1) reduced intracellular lipid accumulation in AML12 hepatocytes by approximately 30% compared to that of vehicle controls. Moreover, it enhanced mitochondrial abundance in a dose-dependent manner, suggesting stimulation of mitochondrial β-oxidation. Our data identify paulobutalipin as a unique microbial natural product that promotes energy metabolism possessing structural complexity and minimal toxicity.

Allosamidin is a metabolite produced by Streptomyces species, known for its inhibitory activity against family 18 chitinases. All known natural congeners of allosamidin are pseudotrisaccharides featuring a cyclopentane moiety fused with an aminooxazoline ring. We discovered a novel allosamidin congener produced by Streptomyces sp. No. 1-5-6, an allosamidin producer newly isolated from soil. Although its yield was very low, its structure was elucidated by NMR and MS analyses as N-acetylallosaminylallosamidin, the first natural allosamidin congener with a pseudotetrasaccharide structure. N-Acetylallosaminylallosamidin inhibited bacterially expressed mouse acidic mammalian chitinase with an IC₅₀ value of 102.3 nM, showing strong activity, albeit slightly weaker than that of allosamidin.

IntroductionLasso peptides are a structurally distinctive class of ribosomally synthesized and post-translationally modified peptides (RiPPs) featuring a threaded rotaxane topology that confers remarkable thermal stability and protease resistance. Citrulassins represent a rare subgroup of lasso peptides distinguished by a citrulline residue generated through peptidylarginine deiminase (PAD)-catalyzed deimination of arginine. Prior to the identification of citrulassin A, such a modification had not been observed in RiPPs, and notably, the PAD-encoding gene is located outside the canonical lasso peptide biosynthetic gene cluster (BGC).MethodsHere, we developed a dual-probe genome-mining strategy that integrates homology searches for both the lasso peptide cyclase (CitC) and a PAD homolog to selectively prioritize candidate producers from the IFB bacterial genome database. Guided by this strategy, fermentation and targeted isolation led to the discovery of citrulassin N (1) from Streptomyces sp. NAX00255.ResultsComprehensive structural elucidation using NMR spectroscopy and tandem mass spectrometry confirmed citrulassin N as a novel citrulline-modified lasso peptid.DiscussionThis study expands the structural diversity of citrulline-containing lasso peptides, demonstrates the utility of a dual-probe genome-mining approach for identifying RiPPs with rare post-translational modifications, and provides a practical framework for the targeted discovery of functionally decorated RiPP natural products.

Grey mould, caused by Botrytis sp., is one of the main phytosanitary constraints in blueberry production, due to its high incidence in the field and post-harvest and the increase in isolates resistant to conventional fungicides. In this context, the present study aimed to determine the potential of strains of the genus Streptomyces spp. isolated from barren soils for the biological control of Botrytis sp. in blueberries. Strains JCH7, JCH5 and JCH3 were isolated from arid soils in the district of Puerto Eten (Peru) and characterized morphologically, biochemically and genetically. Antagonistic activity was evaluated using dual confrontation and well diffusion assays using crude extracts, compared with a commercial synthetic fungicide. The results showed inhibitions greater than 58% in dual confrontation and up to 80.98% in well diffusion, with strain JCH3 standing out for its greater anti-fungal efficacy. Biochemical tests showed the production of key hydrolytic enzymes (cellulases, lipases and proteases), as well as chitinase activity in two of the strains. Genetic identification using the 16S rRNA gene confirmed JCH7 and JCH3 as Streptomyces mutabilis, while JCH5 showed high genetic divergence. Overall, the results confirm the high potential of Streptomyces spp. from fallow soils as biological control agents of Botrytis sp. in blueberries.

Phosphorus is one of the most important nutrients for the growth and development of plants. Although chemical fertilizers supply phosphorus, much of it remains in insoluble forms inaccessible to plants. Numerous applications exist for phosphate-solubilizing bacteria as biological fertilizers in agriculture. By employing sustainable agricultural practices, the use of biofertilizers rather than artificial fertilizers can reduce environmental contamination and increase crop productivity. Here, we explored conserved regions and the gene encoding acid phosphatase (ACPase) and alkaline phosphatase (ALPase) sequences from Streptomyces sp. MMA-NRC, the specimen was separated; genes were sequenced, annotated, and officially recorded in the NCBI GenBank database with unique identification numbers PV646716 and PV646717. Ramachandran’s plot was used to validate the 3D structure of the simulated ACPase and ALPase proteins. The results showed that a significant portion of the amino acid residues were located in the most favored region for the strain Streptomyces NM-NRC, which revealed that 488 and 560 residues, accounting for 94.37 and 93.08% overall quality factor for ACPase and ALPase; respectively. strain 4 F and strain Streptomyces sp. MMA-NRC. Docking studies revealed optimal binding affinities of the ACPase and ALPase proteins with rock phosphate, with high affinity scores for the strain Streptomyces sp. MMA-NRC. Which recorded an affinity score of -110.86 kcal/mol, a confidence score of 0.3137, a ligand RSMD (Å) of 69.31, for wild type strain Streptomyces sp. MMA-NRC ACPase. In addition, recorded affinity score of − 108.55 kcal/mol, confidence score of 0.3039, ligand RSMD (Å) of 33.68, for the wild type strain Streptomyces sp. MMA-NRC ALPase strain. Molecular cloning and expression of the Streptomyces sp. MMA-NRC ACPase and ALPase genes in E. coli DH5α resulted in a recombinant E. coli DH5α pGEM-T-ACPase and E. coli DH5α pGEM-T-ALPase significantly higher available phosphore using ascorbic acid colorimetric method of 52.64 and 57.22 mg/L− 1; respectively after 7 days of incubation, compared to the wild type Streptomyces sp. MMA-NRC, which exhibited a value 35.44 mg/L− 1 after 7 days of incubation. These results suggest that the use of Streptomyces sp. MMA-NRC for phosphatase production seems to be very promising since it has a diverse array of agricultural uses, including plant biofertilizers.

The ascidiacea-derived strain Streptomyces sp. GXX01-02 initially yielded the antifungal polyketide-nucleoside hybrid jawsamycin. To explore further metabolic diversity, the OSMAC strategy was employed, with the rice medium extract notably exhibiting a unique UV signature that suggested the presence of distinct secondary metabolites. This led to the identification of three filipin-type polyene macrolides, pemacromycins A-C (1-3), featuring oxygen bridges between C-13 and C-16 (1, 2) or C-13 and C-17 (3). Their structures were defined by a combination of comprehensive spectroscopic analysis, Kishi's universal NMR database, Newman projections, DP4+ probability analyses, modified Mosher's method, and Mo2(AcO)4-induced circular dichroism. Bioassays revealed that derivatives 1a and 2a exhibited antibacterial activity against Bacillus subtilis with an MIC value of 16 μg/mL, while 1b and 1c showed antifungal effects against Ceratocystis paradoxa and Corynespora cassiicola with MIC values ranging from 16 to 32 μg/mL.

A halotolerant actinobacterial strain, EMB26, was isolated from soil collected from the Salt Pan region of Raigarh, Maharashtra, India. The strain formed dry, powdery colonies with greyish-white aerial mycelia, and Scanning Electron Microscopy revealed a dense, interwoven mycelial network with variable coloration, including grey, white, and pink aerial masses. Phylogenetic analysis based on 16S rRNA sequencing (GenBank Accession No. PP587436) identified EMB26 as closely related to Streptomyces coelicolor, a species well known for its bioactive potential. Physiologically, EMB26 tolerated up to 7% NaCl (optimal 5-6%), efficiently utilized carbohydrates such as dextrose and fructose, resisted multiple antibiotics including chloramphenicol and penicillin G, and produced enzymes such as amylase, protease, and β-galactosidase. Genome analysis (GenBank Accession No. CP177290) revealed extensive biosynthetic potential, with gene clusters predicting metabolites including naphthyridinomycin, curamycin, alkylresorcinols, ectoine, and desferrioxamine. Consistent with these predictions, EMB26 exhibited strong antibacterial activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), as well as Gram-negative bacteria. The strain also effectively disrupted preformed biofilms of Pseudomonas aeruginosa, highlighting a clear correlation between its genomic potential and observed phenotypic bioactivity. Collectively, these features underscore EMB26 as a promising source of novel antimicrobial and bioactive compounds for addressing multidrug-resistant infections.