Streptomyces Research Articles

Antibacterial Activity of Silver Nanoparticles Synthesized from Endophytic Streptomyces sp. CR 13 Isolated from the Roots of Ocimum tenuiflorum L.

In this study, Streptomyces sp. CR 13 from the roots of Ocimum tenuiflorum L. was isolated and characterized using biochemical, morphological and genomic approaches. Silver nanoparticles (AgNPs) were synthesized extracellularly using cell-free extract and characterized with UV-vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), EDX, DLS and zeta potential techniques. The maximum peak of UV-visible spectroscopy was observed at 425 nm and the TEM images revealed that the nanoparticles were spherical in shape and ranged in size from 18 to 21 nm. DLS analysis revealed particles with an average diameter of 147.9 nm. The zeta potential analysis of biosynthesized AgNPs showed a peak at -35.2 mV, indicating their high stability. Moreover, AgNPs synthesized by endophytic Streptomyces showed significant antimicrobial activity against Escherichia coli, Klebsiella pneumonia and Stphylococcus aureus.

Purification and Characterization of a Small Thermostable Protease from Streptomyces sp. CNXK100.

Proteases derived from Streptomyces demonstrate numerous commendable properties, rendering it extensively applicable in biotechnology and various industrial sectors. This study focused on the purification and characterization of the thermostable protease obtained from Streptomyces sp. CNXK100. The purified protease exhibited an estimated molecular weight of 27 kDa, with optimal activity at 75°C and pH 8.0. Notably, the enzyme remained active even without any metal ions and fully active in the presence of Na+, K+, Mg2+, and Cu2+metal ions. The kinetic parameters were determined with a KM value of 3.13 mg/ml and a Vmax value of 3.28 × 106 U/mg. Furthermore, the protease has demonstrated notable stability when subjected to a treatment temperature of up to 65°C for 60 minutes, and across a broad pH range extending from 5.0 to 10.0. This protease also demonstrated resilience against a spectrum of harsh conditions, including exposure to organic solvents, surfactants, bleaching agents, and proteolytic enzymes. Additionally, the enzyme maintained its activity following treatment with commercial detergents, accomplishing complete thrombus lysis at a concentration of 2.50 mg/ml within 4 hours. Remarkably, the protease exhibited stability in terms of activity and protein concentration for 70 days at 4°C. These findings underscore the potential industrial applications of the thermostable protease from Streptomyces sp. CNXK100.

Integrative Genomics and Bioactivity-Guided Isolation of Novel Antimicrobial Compounds from Streptomyces sp. KN37 in Agricultural Applications.

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.

Metabolic Blockade-Based Genome Mining of Sea Anemone-Associated Streptomyces sp. S1502 Identifies Atypical Angucyclines WS-5995 A-E: Isolation, Identification, Biosynthetic Investigation, and Bioactivities.

Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to be an effective strategy to accelerate the discovery of natural products from both terrestrial and marine microorganisms. Here, the metabolic blockade-based genome mining strategy was applied to the discovery of other metabolites in a sea anemone-associated Streptomyces sp. S1502. We constructed a mutant Streptomyces sp. S1502/Δstp1 that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster (wsm) of the angucyclines was identified through gene knock-out and heterologous expression studies. The biosynthetic pathways of WS-5995 A-E were proposed, the roles of some tailoring and regulatory genes were investigated, and the biological activities of WS-5995 A-E were evaluated. WS-5995 A has significant anti-Eimeria tenell activity with an IC50 value of 2.21 μM. The production of antibacterial streptopyrroles and anticoccidial WS-5995 A-E may play a protective role in the mutual relationship between Streptomyces sp. S1502 and its host.

Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase.

Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable of coordinating cupric ions draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, the chm biosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. The chm cluster was localized to a ~31 kb DNA region, consisting of 19 open reading frames that encode five nonribosomal peptide synthetases (ChmHIJLO), one modular polyketide synthase (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA'CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100 chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach.

Benastatin K, a chlorinated benastatin-related antibiotic from Streptomyces sp. HGTA384.

Benastatin K (1), a new chlorinated benastatin derivative, was isolated from the culture broth of the actinomycete Streptomyces sp. HGTA384. The structure of 1 was determined on the basis of spectroscopic analysis, including 1D and 2D NMR, as well as HRESI-MS, UV and IR, and comparison with data reported in the literature. Compound 1 and benastatins A and B exhibited inhibitory activity against Micrococcus luteus (MIC 7.8, 31.3, and 3.9 μM, respectively), and IgE-mediated β-hexosaminidase release in RBL-2H3 cells with IC50 values of 42, 79, and 19 μM, respectively.

Anti-Melanogenic Activity of Undecylprodigiosin, a Red Pigment Isolated from a Marine Streptomyces sp. SNA-077.

Bioassay and HPLC-UV guided fractionations of the crude extract of marine-derived Streptomyces sp. SNA-077 have led to the isolation of a red pigment, undecylprodigiosin (1). The chemical structure of undecylprodigiosin (1) was revealed by the interpretation of NMR and mass spectroscopic (MS) data. Further, anti-melanogenic effects of undecylprodigiosin (1) were investigated. First, the melanin contents of undecylprodigiosin (1)-treated B16 cells were evaluated. Furthermore, undecylprodigiosin (1) significantly inhibited the key enzymes involved in melanogenesis, including tyrosinase, tyrosinase related protein-1 (TYRP-1), and dopachrome tautomerase (DCT). The mRNA and protein expression levels of Microphthalmia-associated transcriptian factor (MiTF), a critical transcription factor for tyrosinase gene expression, were also suppressed by undecylprodigiosin (1) treatment in B16 analyses. Collectively, our results suggest for the first time that undecylprodigiosin (1), a potent component isolated from an extract of marine Streptomyces sp. SNA-077, critically exerts the anti-melanogenic ability for melanin synthesis.

Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity.

Actinomycetes are prolific producers of natural products, particularly antibiotics. However, a significant proportion of its biosynthetic gene clusters (BGCs) remain silent under typical laboratory conditions. This limits the effectiveness of conventional isolation methods for the discovery of novel natural products. Genetic interventions targeting the activation of silent gene clusters are necessary to address this challenge. Streptomyces antibiotic regulatory proteins (SARPs) act as cluster-specific activators and can be used to target silent BGCs for the discovery of new antibiotics. In this study, the expression of a previously uncharacterized SARP protein, Syo_1.56, in Streptomyces sp. RK18-A0406 significantly enhanced the production of known antimycins and led to the discovery of 12 elasnins (1-12), 10 of which were novel. The absolute stereochemistry of elasnin A1 was assigned for the first time to be 6S. Unexpectedly, Syo_1.56 seems to function as a pleiotropic rather than cluster-specific SARP regulator, with the capability of co-regulating two distinct biosynthetic pathways, simultaneously. All isolated elasnins were active against wild-type and methicillin-resistant Staphylococcus aureus with IC50 values of 0.5-20 μg/mL, some of which (elasnins A1, B2, and C1 and proelasnins A1, and C1) demonstrated moderate to strong antimalarial activities against Plasmodium falciparum 3D7. Elasnins A1, B3, and C1 also showed in vitro inhibition of the metallo-β-lactamase responsible for the development of highly antibiotic-resistant bacterial strains.

Effective biological control of southern blight of Dendrobium officinale by Streptomyces sp. MEPF0303

Southern blight is a common and devastating disease adversely affecting the yield and quality of cultivated Dendrobium officinale plants. The pathogens responsible for this disease are Sclerotium delphinii and S. rolfsii, although S. delphinii is more pathogenic than S. rolfsii. Plant endophytes are potential sources of biological control agents. In this study, 18 microbial strains were isolated from wild Dendrobium shixingense plants (e.g., Streptomyces, Bacillus, and Trichoderma), among which strain MEPF0303 significantly inhibited S. delphinii mycelial growth. Based on 16S rRNA gene sequence, this strain was identified as Streptomyces sp. In addition, the volatile organic compounds and cell-free supernatant of MEPF0303 had significant inhibitory effects on S. delphinii growth. Moreover, MEPF0303 effectively controlled southern blight of D. officinale. A total of 1,797 differentially expressed genes were identified by a comparative transcriptome analysis of S. delphinii mycelia treated with MEPF0303 and the untreated control mycelia. Strain MEPF0303 significantly altered the expression of genes related to cell membrane morphological development and integrity, pathogenicity, energy metabolism, and oxidative stress responses. Furthermore, the transcriptome sequencing results were validated by analyzing gene expression via a quantitative real-time polymerase chain reaction. The study results showed that MEPF0303 can inhibit the growth and pathogenicity of S. delphinii, with potential implications for the biological control of southern blight of D. officinale.

The Discovery of Weddellamycin, a Tricyclic Polyene Macrolactam Antibiotic from an Antarctic Deep-Sea-Derived Streptomyces sp. DSS69, by Heterologous Expression.

Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 μg/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 μg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 µM.

Discovery of a Novel Chromone Enantiomer and the Precursors of Nonactic Acid from the Coral-Reef-Derived Streptomyces sp. SCSIO 66814.

Three pairs of enantiomers (1-3)-the new 12R-aloesol (1a) and two new fatty acids (2 and 3)-and one new natural product (4) together three known compounds (5-7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2-5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals.

Whole Genome Analysis of Streptomyces spp. Strains Isolated from the Rhizosphere of Vitis vinifera L. Reveals Their Role in Nitrogen and Phosphorus Metabolism

The rhizospheric microorganisms of agricultural crops play a crucial role in plant growth and nutrient cycling. In this study, we isolated two Streptomyces strains, Streptomyces sp. LM32 and Streptomyces sp. LM65, from the rhizosphere of Vitis vinifera L. We then conducted genomic analysis by assembling, annotating, and inferring phylogenomic information from the whole genome sequences. Streptomyces sp. strain LM32 had a genome size of 8.1 Mb and a GC content of 72.14%, while Streptomyces sp. strain LM65 had a genome size of 7.3 Mb and a GC content of 71%. Through ANI results, as well as phylogenomic, pan-, and core-genome analysis, we found that strain LM32 was closely related to the species S. coelicoflavus, while strain LM65 was closely related to the species S. achromogenes subsp. achromogenes. We annotated the functional categories of genes encoded in both strains, which revealed genes involved in nitrogen and phosphorus metabolism. This suggests that these strains have the potential to enhance nutrient availability in the soil, promoting agricultural sustainability. Additionally, we identified gene clusters associated with nitrate and nitrite ammonification, nitrosative stress, allantoin utilization, ammonia assimilation, denitrifying reductase gene clusters, high-affinity phosphate transporter and control of PHO regulon, polyphosphate, and phosphate metabolism. These findings highlight the ecological roles of these strains in sustainable agriculture, particularly in grapevine and other agricultural crop systems.

Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism

BackgroundIsatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs.ResultsHere we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date.ConclusionIn Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

Genome-guided discovery of two undescribed 6,6-spiroketal polyketides and stereochemical correction of bafilomycins P and Q from the marine-derived Streptomyces sp. SCSIO 66814

Bafilomycins are macrocyclic polyketides with intriguing structures and therapeutic value. Genomic analysis of Streptomyces sp. SCSIO 66814 revealed a type I polyketide synthase biosynthetic gene cluster (BGC), namely blm, which encoded bafilomycins and featured rich post-modification genes. The One strain many compounds (OSMAC) strategy led to the discovery of six compounds related to the blm BGC from the strain, including two previously undescribed 6,6-spiroketal polyketides, streptospirodienoic acids D (1) and E (2), and four known bafilomycins, bafilomycins P (3), Q (4), D (5), and G (6). The structures of 1 and 2 were determined by extensive spectroscopic analysis, quantum calculation, and biosynthetic analysis. Additionally, the absolute configurations of the 6/5/5 tricyclic ring moiety containing six consecutive chiral carbons in the putative structures of 3 and 4 were corrected through NOE analysis, DP4+ calculation, and single-crystal X-ray diffraction data. Bioinformatic analysis uncovered a plausible biosynthetic pathway for compounds 1–6, indicating that both streptospirodienoic acids and bafilomycins were derived from the same blm BGC. Additionally, sequence analysis revealed that the KR domains of module 2 from blm BGC was B1-type, further supporting the configurations of 1–4. Notably, compounds 3 and 4 displayed significant cytotoxic activities against A-549 human non-small cell lung cancer cells and HCT-116 human colon cancer cells.

Application of Cas12j for Streptomyces Editing.

In recent years, CRISPR-Cas toolboxes for Streptomyces editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Streptococcus pyogenes Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of Streptomyces strains. This study explored the first use of Acidaminococcus sp. Cas12j, a hypercompact Cas12 subfamily, for genome editing in Streptomyces and its potential in activating silent biosynthetic gene clusters (BGCs) to enhance natural product synthesis. While the editing efficiencies of Cas12j were not as high as previously reported efficiencies of Cas12a and Cas9, Cas12j exhibited higher transformation efficiencies compared to SpCas9. Furthermore, Cas12j demonstrated significantly improved editing efficiencies compared to Cas12a in activating BGCs in Streptomyces sp. A34053, a strain wherein both SpCas9 and Cas12a faced limitations in accessing the genome. Overall, this study expanded the repertoire of Cas proteins for genome editing in actinomycetes and highlighted not only the potential of recently characterized Cas12j in Streptomyces but also the importance of having an extensive genetic toolbox for improving the editing success of these beneficial microbes.

New Analogues of Amides and Quinolinones Produced by Streptomyces sp. YIM S01983.

Streptomide (1), a new amide analogue, streptomynone (2), a new quinolinone, and ten known compounds including three aliphatic acids (3-5), two amides (6-7), four cyclic dipeptides (8-11), and an adenosine (12) were isolated from the fermentation broth of Streptomyces sp. YIM S01983 isolated from a sediment sample collected in Bendong Village, Huadong Town, Chuxiong, China. Their structures were determined by analysis of the 1D/2D-NMR and HR-ESI-MS spectra. Compound 12 presented weak antimicrobial activities against Candida albicans and Aligenes faecalis (MIC=64 μg/mL). Compounds 7 and 12 showed weak cytotoxic activity against MHCC97H.

Culture optimization of Streptomyces sp. KRA16-334 for increased yield of new herbicide 334-W4.

This study aimed to isolate actinomycetes that exhibit strong herbicidal activity, identify compounds active against weeds, and researching methods to improve the production of these compounds through culture optimization to establish a foundation for the development of environmentally friendly bioherbicides. 334-W4, one of the herbicidal active substances isolated from the culture broth of Streptomyces sp. KRA16-334, exhibited herbicidal activity against various weeds. The molecular formula of 334-W4 was determined to be C16H26N2O6, based on ESI-MS (m/z) and 1H and 13C NMR spectral data. It had molecular weight 365.1689 [M+Na] and 343.1869 [M+H], indicating the presence of the epoxy-β-aminoketone moiety based on HMBC correlations. Additionally, selective culture was possible depending on the addition of trifluoroacetic acid (TFA) during culture with GSS medium. Experiments confirmed that exposure of the KRA16-334 strain to UV irradiation (254 nm, height 17 cm) for 45 seconds improved the yield of the active substance (334-W4) by over 200%. As a result of examining yields of active materials of four mutants selected through optimization of culture conditions such as temperature, agitation, and initial pH, the yield of one mutant 0723-8 was 264.7 ± 12.82 mg/L, which was 2.8-fold higher than that of wild-type KRA16-334 at 92.8 ± 5.48 mg/L.

Harnessing the potential of a novel lignin-degrading Streptomyces sp. MS-S2 from wood-feeding termite for malachite green decolorization and detoxification

Lignin and synthetic dyes share complex structural similarities and relevant management difficulties, which should be effectively addressed towards environmental sustainability. Under this scope, the quest for oxidative enzyme-producing microorganisms with a view to efficiently valorizing organic pollutants is of utmost importance. The intestinal bacteria of wood-feeding termites represent a unique source of valuable enzymes. The decolorization efficiency of five different dyes, including malachite green (MG), methyl violet, anihiline blue, reactive red, and reactive blue, after 12 h of degradation by the MS-S2 bacterial strain was recorded to be 98.2, 17.5, 8.7, 4.6, and 3.28%, respectively. Several physico-chemical parameters were then optimized to accelerate MG degradation, including pH, temperature, glucose, and yeast extract concentration. Streptomyces sp. strain MS-S2 completely decolorized MG (50 mg/L) within 2 h under optimized conditions when the cultivation medium was amended with 5 g/L glucose and 0.08 g/L yeast extract at pH 8 and incubated at 28 °C. After MG degradation, the enzyme activities of manganese peroxidase (4.605 U/L) and laccase (45.185 U/L) were estimated. To comprehend the degradation process of MG by the MS-S2 strain, UV-Vis spectroscopy, Fourier transform infrared (FTIR), and gas chromatography-mass spectrometry (GC-MS) analyses were carried out to ascertain the possible degradation mechanism. The metabolites identified, such as 2,6-Bis (tert-butyl) phenol and [4-(dimethylamino) phenyl] phenyl, suggest that MG was broken down into less toxic compounds for further degradation. MS-S2 exhibited outstanding characteristics that could make it suitable for the bioremediation of MG dye in an industrial setting.

Dual Role Of Streptomyces Strains: Reduction of Aeromonas Counts In Both Culture Water And The Intestine, And Growth Enhancement of Discus Fish (Symphysodon sp.)

Discus fish (Symphysodon sp.) brings the largest export turnover to the ornamental fish industry in Vietnam. The intensive farming of discus fish to meet export market demand leads to a higher risk of bacterial disease, with Aeromonas being the main infectious agent. Continuous antibiotic use exerts selective pressure, fostering the emergence of antibiotic-resistant bacterial strains capable of causing diseases in fish. Streptomyces sp. considered as probiotics with the role of replacing antibiotics in applications such as promoting growth, improving survival rates, and controlling pathogenic bacteria in aquaculture. The primary objective of this study was to assess the influence of Streptomyces sp. on the growth performance, and Aeromonas density in intestine of discus fish and in culture water. Discus fish fed diets containing Streptomyces sp. TM1, TM7, and TM22 showed significantly higher growth parameters (45.24 - 58.72% of final body weight - FBW, 14.8 - 16.66% of final body length -FBL, 16.03 – 20.87 % of specific growth rate of weight – SGRW, 10.79 - 12.05 % of specific growth rate of length – SGRL, and 41.48 – 46.54 % of feed conversion ratio – FCR) compared to the control. Additionally, total Aeromonas densities of the fish treated with TM1, TM7, and TM22 showed a notable decrease compared to the control treatment in the rearing water with log CFU/ml values of 4.517 (Control), 2.554 (TM1), 2.571 (TM7), 2.222 (TM22) and in the intestines of fish with log CFU/g values of 5.597 (Control), 3.828 (TM1), 3.806 (TM7), 3.648 (TM22). Streptomyces sp. TM1, TM7, and TM22 could decreased total Aeromonas count in the gut of discus fish and in the rearing water, and boost the growth performance of discus fish (Symphysodon sp.).

Bioactive Secondary Metabolites Produced by the Hadal Actinomycete Streptomyces sp. SY1414 Isolated from the Mariana Trench-derived Sediment

Background:: Accumulated investigations have demonstrated that the Mariana Trench is enriched in microorganisms. However, the diversity of structures and bioactivities of the secondary metabolites produced by the Mariana Trench-associated microorganisms is poorly known, which needs to be intensively investigated. Objective:: This study aimed to investigate the bioactive secondary metabolites produced by a Mariana Trench-derived actinomycete Streptomyces sp. SY1414 was cultured in BY medium, which was chosen from four different media based on the diversity of secondary metabolites. Methods:: A combination of different column chromatographs and HPLC was applied for the separation and purification of the secondary metabolites. The structures of the isolated compounds were determined mainly based on their NMR data, optical rotation values, and the comparison with the reference data, and the Sulforhodamine B (SRB) method was used to evaluate the anti-glioma activity of isolated compounds. Results:: Four different types of compounds were isolated from the large culture of strain Streptomyces sp. SY1414 in BY medium, including a benzoquinoline alkaloid, actinophenanthroline C (1), a benzamide, (2E,4E)-5-(3-hydroxyphenyl)-penta-2,4-dienamide (2), a cyclopeptide, valinomycin (3), and four macrolides of bafilomycin D (4), bafilomycin A2 (5), bafilomycin W (6), and C(19), C(21)- O-methyl-bafilomycin A1 (7). Actinophenanthroline C (1), bafilomycin D (4), bafilomycin A2 (5), and bafilomycin W (6) displayed significant anti-glioma activities with IC50 values ranging from 1.62 to 8.20 μM for U87MG cells and 2.45 to 3.89 μM for U251. The anti-gliomas of actinophenanthroline C (1) was reported for the first time. Conclusion:: The hadal actinomycete Streptomyces sp. SY1414 in BY medium produced four different types of secondary metabolites with significant anti-glioma activity, which enriched the diversity of structures and bioactivities of the Mariana Trench-associated natural products.