Streptomyces Research Articles

Mining Translation Inhibitors by a Unique Peptidyl-Aminonucleoside Synthetase Reveals Cystocin Biosynthesis and Self-Resistance

Puromycin (Puro) is a natural aminonucleoside antibiotic that inhibits protein synthesis by its incorporation into elongating peptide chains. The unique mechanism of Puro finds diverse applications in molecular biology, including the selection of genetically engineered cell lines, in situ protein synthesis monitoring, and studying ribosome functions. However, the key step of Puro biosynthesis remains enigmatic. In this work, pur6-guided genome mining is carried out to explore the natural diversity of Puro-like antibiotics. The diversity of biosynthetic gene cluster (BGC) architectures suggests the existence of distinct structural analogs of puromycin encoded by pur-like clusters. Moreover, the presence of tRNACys in some BGCs, i.e., cst-like clusters, leads us to the hypothesis that Pur6 utilizes aminoacylated tRNA as an activated peptidyl precursor, resulting in cysteine-based analogs. Detailed metabolomic analysis of Streptomyces sp. VKM Ac-502 containing cst-like BGC revealed the production of a cysteinyl-based analog of Puro—cystocin (Cst). Similar to puromycin, cystocin inhibits both prokaryotic and eukaryotic translation by the same mechanism. Aminonucleoside N-acetyltransferase CstC inactivated Cst, mediating antibiotic resistance in genetically modified bacteria and human cells. The substrate specificity of CstC originated from the steric hindrance of its active site. We believe that novel aminonucleosides and their inactivating enzymes can be developed through the directed evolution of the discovered biosynthetic machinery.

Pyrimidine Nucleosides, Benzoic Acid Derivative and Bipyridinefrom the Marine-Derived Streptomyces sp. DS52.

Fourteen new compounds were isolated from marine-derived Streptomyces sp. DS52, including twelve pyrimidine nucleosides (1-12), one benzoic acid derivative (13) and one dipyridine derivative (14). Additionally, twenty-eight known compounds (15-42) were identified. The structures of all compounds were elucidated through extensive analysis of NMR spectroscopic and HRESIMS data. ECD calculations were employed to investigate the configurations of compounds 1, 2 and 4-13. Bioactivity evaluations of all of the compounds showed that compounds 6, 7, 9, 11, 15, 33-38, 41, and 42 exhibited cytotoxicity against HCT-116 human colon cancer cell lines and MDA-MB-231 human breast cancer cell lines, with IC50 values ranging from 0.73 ± 0.06 to 17.44 ± 0.53 μM and from 1.11 ± 0.06 to 18.51 ± 3.07 μM, respectively. Notably, compound 41 exhibited significant cytotoxicity against the HCT-116 and MDA-MB-231 human cancer cell lines with IC50 values of 0.73 ± 0.06 and 1.11 ± 0.06 μM, respectively.

Deciphering the biodegradation mechanism of 3,6-dichlorocarbazole using a novel isolate for its implication in bioaugmentation

This study reported a newly isolated strain, Streptomyces sp. FW-32, which showed good ability to degrade 3,6-dichlorocarbazole (3,6-DCCZ). The maximum degradation efficiency of 3,6-DCCZ reached 86.78 % within 5 d at pH of 7.6, glucose concentration of 5.0 g/L, temperature of 33 °C, and 3,6-DCCZ initial concentration of 1.0 mg/L. In total, five biodegradation products were detected, indicating that 3,6-DCCZ was mainly transformed via dechlorination, oxidation, and aromatic ring cleavage. Proteomic analysis suggested that haloacid dehalogenase, glutathione S-transferase family protein, cytochrome P450s, pentachlorophenol monooxygenase, hydroxylase, and several dioxygenases were involved in 3,6-DCCZ biotransformation. Glutathione peroxidase, catalases, catalase − peroxidase, thioredoxin, thioredoxin reductase, and thioredoxin-dependent peroxiredoxin were induced to resist 3,6-DCCZ stress. Molecular docking revealed that 3,6-DCCZ exhibited an affinity for the potential proteins involved in 3,6-DCCZ biodegradation and stress response. Furthermore, the biotreatment of 3,6-DCCZ with the strain FW-32 might have contributed to the reduction in the aquatic toxicity of 3,6-DCCZ. The strain FW-32 efficiently synergized with certain indigenous microorganisms, consequently accelerating the removal of 3,6-DCCZ from the water–sediment system. Overall, these findings shed a new light on the mechanisms underlying the microbial transformation of 3,6-DCCZ, suggesting that Streptomyces sp. FW-32 exhibits considerable potential for the bioaugmentation of 3,6-DCCZ-contaminated aquatic environments.

Exploring northeast India’s culturable soil Actinomycetia for potent antibacterial agents against gram-positive bacterial pathogens of clinical importance

This study investigated the isolation and bioactivity of Actinomycetia from the soil of Northeast India, a region rich in microbial diversity. A total of 187 presumptive Actinomycetia isolates were obtained and 53 were found to exhibit antimicrobial properties. Phylogenetic analysis based on 16 S rRNA gene sequencing revealed that the isolates were predominantly from the genus Streptomyces. Among these, the strain Streptomyces sp. NP14 (ANP14ARS) demonstrated specific and significant antimicrobial activity against gram-positive bacterial pathogens. The strain was further assayed against a panel of clinically important bacterial pathogens including Methicillin-resistant Staphylococcus aureus (MRSA). Its antimicrobial activity was confirmed using disc diffusion and membrane disruption assay, and its minimum inhibitory concentration was determined to be ≥ 3.12 ± 0.5 µg/ml against MRSA. Chemical analyses using FTIR and GC-MS identified key bioactive compounds, including Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)- and Phenol 3,5-bis(1,1-dimethylethyl), known for their antimicrobial properties. Toxicity studies against animal liver cell lines indicated that the ethyl acetate extract was non-toxic at concentrations below 125 µg/mL, compared to Vancomycin, which was found to be hepatotoxic at similar concentrations. These findings highlight the potential of ANP14ARS as a source of bioactive natural products that is specific towards priority pathogens such as MRSA.

Antimicrobial, Antioxidant Activity of Ethyl Acetate Extract of Streptomyces sp. PERM2, its Potential Modes of Action and Bioactive Compounds

Background: Microorganisms belonging to Streptomyces sp. are Gram-positive bacteria known for their unsurpassed capacity for the production of secondary metabolites with diverse biological activities. The aim of this study was to evaluate the antimicrobial and antioxidant properties of ethyl acetate Streptomyces sp. PERM2 extract, its potential modes of action and bioactive secondary metabolites. Results: The ethyl acetate PERM2 extract showed antimicrobial activity more pronounced on both Gram-positive and Gram-negative bacteria and fungi with a Minimum Inhibitory Concentration value (MIC) of 0.5 mg/mL and Minimum Bactericidal Concentration (MBC) of 2 - 4 mg/mL against bacterial pathogens. MIC value against pathogenic fungi was 2 mg/mL and Minimum Fungicidal Concentration (MFC) of 0.01 - 0.05 mg/mL against pathogenic fungi. PERM2 crude extract showed the ability to inhibit bacteria cell wall synthesis at 0.5 and 1 MIC. The extract was found to possess dose-dependent 2,2-Diphenyl-picrylhadrazyl (DPPH) free radical scavenging and Ferric reducing activity. The gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of three major compounds identified as 9,12-octadecadienoic acid (Z, Z) (29.75%), tridecyl trifluoroacetate (24.82%) and 1-(+)-ascorbic acid 2, 6-dihexadecanoate (22.34%). The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of 22 non-volatile metabolites in PERM2 extract and only the compound 3, 30-O-dimethylellagic acid was identified. Conclusion: The results of this study indicate that ethyl acetate Streptomyces sp. PERM2 extract possesses antibacterial, antifungal, and antioxidant activities; inhibits bacteria cell wall and protein synthesis; and contains significant bioactive secondary metabolites which could be used as an alternative to multi-resistance antibiotics.

Crystal structure of β-d-galactofuranosidase from Streptomyces sp. JHA19 in complex with an inhibitor provides insights into substrate specificity.

d-Galactofuranose (Galf) is widely distributed in glycoconjugates of pathogenic microbes. β-d-Galactofuranosidase (Galf-ase) from Streptomyces sp. JHA19 (ORF1110) belongs to glycoside hydrolase (GH) family 2 and is the first identified Galf-specific degradation enzyme. Here, the crystal structure of ORF1110 in complex with a mechanism-based potent inhibitor, d-iminogalactitol (Ki = 65 μm) was solved. ORF1110 binds to the C5-C6 hydroxy groups of d-iminogalactitol with an extensive and integral hydrogen bond network, a key interaction that discriminates the substrates. The active site structure of ORF1110 is largely different from those of β-glucuronidases and β-galactosidases in the same GH2 family. A C-terminal domain of ORF1110 is predicted to be a carbohydrate-binding module family 42 that may bind Galf. The structural insights into Galf-ase will contribute to the investigation of therapeutic tools against pathogens.

An Overview of Lsr2 Repressor Effect in Streptomyces spp. Secondary Metabolism.

The genus Streptomyces is one of the largest producers of secondary metabolites with bioactive properties of interest. However, many of the genes involved in synthesizing these compounds are silenced under laboratory conditions. One of the strategies used to activate these metabolic pathways is the elimination of repressor genes, which prevent the transcription of other genes. In this work, the lsr2 gene has been selected for study since it is a repressor with a preference for binding to AT-rich regions, which makes it exert its effect especially on those horizontally transferred gene sequences that have a very different GC content to the core Streptomyces spp. genome. Therefore, the effects of the deletion of this gene are observed, and, in addition, a mapping of the potential binding sites of Lsr2 in Streptomyces spp. genomes is proposed. As a result of this gene knockout, the production of various secondary metabolites is overproduced and/or activated, which suggests that the study of this regulator can be interesting in the field of natural product discovery.

Anti-inflammatory Fatty Acid Derivatives From Mangrove-derived Actinomycetes Streptomyces sp.

Mangrove-derived actinomycetes are prolific chemical sources of complex and novel natural products, providing an excellent chance for new drug discovery. The chemical investigation of the mangrove-derived Streptomyces sundarbansensis 06037, led to the discovery of two previously undescribed enone fatty acids (1-2), one new phenylpropionate derivate (3), along with the isolation of the ten known components (4-13). Those chemical structures of isolates were elucidated on the basis of the analysis of diverse spectroscopic data. Initial anti-inflammatory tests of 1-3 in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells revealed that compound 1 possess significant inhibitory effect on the production of Nitro oxidase (NO), with the IC50 value around 15.33±1.32 μM, together with the suppression of NF-κB phosphorylation and reducing the release of oxygen species (ROS) in RAW 264.7 macrophages, those results indicated that compound 1 may exert its anti-inflammatory activity through a reduction in ROS level and the suppression of NF-κB activation pathway.

Characterization of Antibacterial Compounds from Marine Sponge-associated Streptomyces spp. against Some Pathogenic Bacteria

The increasing trend of antibiotic resistance among pathogenic bacteria is a worldwide problem. Streptomyces produce a number of bioactive compounds such as antibacterial. This study aimed to investigate the effect of different media and incubation time in increasing the antibacterial activity of marine sponge-associated Streptomyces spp. and characterize antibacterial compounds of marine sponge-associated Streptomyces spp. against pathogenic bacteria. Among the three tested media and some days of incubation times, Streptomyces spp. produce more antibacterial activity when grown using modified molasses medium at 15 days incubation. The ethyl acetate extracts of Dbi28t exhibited a significant inhibitory zone against Extended Spectrum β-Lactamase (ESBL)-producing Escherichia coli, Providencia rettgeri then followed by Proteus mirabilis and Pseudomonas putida and the results were higher than some commercial antibiotics. This study has identified nine antibacterial compounds in Dbi28t using Liquid Chromatography-tandem Mass Spectrometric (LC-MS/MS) analysis, with the most abundance belonging to pumilacidin A, then followed by pumilacidin B, surfactin B, surfactin A, phenazostatin B, chalcomycin B, neopyrrolomycin C, saquayamycin A and saphenamycin. This work provides the first report from a Streptomyces sp. Dbi28t produced pumilacidin, surfactin and other bioactive compounds with the modified molasses medium for optimization of characterization of its antibacterial compounds.

Isolation and selection of spore-forming bacilli with potential for self-healing of concrete

The self-healing of concrete through the use of bacteria is an ecological, sustainable, and environmentally friendly method that can replace time-consuming and costly repairs. The aim of this research was to isolate and select spore-forming bacilli with potential for concrete self-healing. Soil samples from the limestone mines of Simbal, Trujillo, La Libertad, Peru were used. These samples were processed to primarily isolate spore-forming bacteria. The self-healing potential of these bacteria was evaluated through their ability to produce the urease enzyme, grow at an alkaline pH, and produce calcium carbonate crystals in a culture medium with urea and CaCl2 at pH 8.0. The produced crystals were visualized with scanning electron microscopy and their calcium content was confirmed through EDS analysis. The isolated bacteria were identified by 16 S rRNA gene amplification by PCR as Bacillus sp and Streptomyces sp. It was observed that Bacillus sp. produces CaCO3 crystals with vaterite morphology, while Streptomyces sp. produces rhombohedral calcite crystals. It is concluded that the isolated bacteria have the potential to be used in concrete self-healing processes.

Genomic Comparisons Revealed the Key Genotypes of Streptomyces sp. CB03234-GS26 to Optimize Its Growth and Relevant Production of Tiancimycins.

Strain robustness and titer improvement are major challenges faced in the industrial development of natural products from Streptomyces. Tiancimycins (TNMs) produced by Streptomyces sp. CB03234 are promising anticancer payloads for antibody-drug conjugates, but further development is severely limited by the low titer of TNMs. Despite many efforts to generate various TNMs overproducers, the mechanisms underlying high TNMs production remain to be explored. Herein, genome resequencing and genomic comparisons of different TNMs overproducers were conducted to explore the unique genotypes in CB03234-GS26. Four target genes were selected for further bioinformatic analyses and genetic validations. The results indicated that the inactivation of histidine ammonia-lyase (HAL) showed the most significant effect by blocking the intracellular degradation of histidine to facilitate relevant enzymatic catalysis and thus improve the production of TNMs. Additionally, the potassium/proton antiporter (P/PA) was crucial for intracellular pH homeostasis, and its deficiency severely impaired the alkaline tolerance of the cells. Subsequent pan-genomic analysis suggested that HAL and P/PA are core enzymes that are highly conserved in Streptomyces. Therefore, HAL and P/PA represented novel targets to regulate secondary metabolism and enhance strain robustness and could become potential synthetic biological modules to facilitate development of natural products and strain improvement in Streptomyces.

Taxonomic characterization and secondary metabolite production of newly isolated Streptomyces sp. MC12

An actinobacterium newly isolated from soil during a screening study was identified as Streptomyces sp. MC12 (GenBank accession number: PP757795) based on 16S rRNA analysis. For secondary metabolite production, fermentation was carried out in ISP 2 broth at 30°C, pH 7.3, for seven days under shaking conditions at 180 rpm. As a result of fermentation studies, the antagonistic effect of the crude extract, obtained through ethyl acetate extraction, against various microorganisms was determined. The MIC values of the extract against Staphylococcus aureus and Escherichia coli were 101.3 µg/mL and 153.6 µg/mL, respectively. It was also found to exhibit strong antifungal activity against Penicillium spp. Streptomyces sp. MC12, which displays both antifungal and antibacterial properties, is considered a potential secondary metabolite producer for future studies, particularly in pharmacology and the biocontrol of fungal pathogens.

A new benzodioxole derivative from the marine-derived Streptomyces sp. SYPHU 0002

a new benzodioxole derivative 1,3-benzodioxole-2-one-4-N-methylcarboxylamide (1), two new natural products N-(aminocarbonyl)-2,3-dimethoxy-benzamide (2) and 2,3-dimethoxy-N-methylbenzamide (3), along with eight known compounds (4-11), were isolated from the marine-derived Streptomyces sp. SYPHU 0002. The structures of compounds 1-11 were determined through comprehensive spectroscopic analyses, including HRESIMS, 1D and 2D NMR. Compound 9 showed weak antibacterial activity against Bacillus pumilus with the MIC value of 64 μg mL−1.

Harnessing the microbial interactions from Apocynum venetum phyllosphere for natural product discovery

Natural products (NPs) afforded by living-beings, especially by microscopic species, represent invaluable and indispensable reservoirs for drug leads in clinical practice. With the rapid advancement in sequencing technology and bioinformatics, the ever-increasing number of microbial biosynthetic gene clusters (BGCs) were decrypted, while a great deal of BGCs remain cryptic or inactive under standard laboratory culture conditions. Addressing this dilemma requires innovative tactics to awaken quiescence of BGCs by releasing the potential of microbial secondary metabolism for mining novel NPs. In this study, a universal strategy was proposed to induce the expression of silent BGCs by leveraging the dynamic interactions among coexisting microbial neighbors within a microbiota. This approach involves the deconstruction/reconstruction of binary interactions among the coexisting neighbors to create a pipeline for BGCs arousing. Coupled with the acquisition of 2,760 microbial individuals from the Apocynum venetum (Luobuma, LBM) phyllosphere in a successive dilution procedure, 44 culturable isolates were screened using binary interaction, in which 12.6% pairs demonstrated potent mutual interacting effects. Furthermore, after selecting the most four promising isolates, a full-scale metabolic inspection was conducted, in which 25.3% of the interacting pairs showcased significant metabolomic variations with de-cryptic activities. Notably, with the aid of visualization of IMS technology, one of the physiologically functional entities, the bactericidal agent resistomycin, was elucidated from the core interacting pair between the co-culture of the Streptomyces sp. LBM_605 and the Rhodococcus sp. LBM_791. This study highlights the intrinsic interactions among coexisting microorganisms within a phyllosphere microbiota as novel avenues for exploring and harnessing NPs.

Isolation, Antibacterial Activity and Molecular Identification of Avocado Rhizosphere Actinobacteria as Potential Biocontrol Agents of Xanthomonas sp.

Actinobacteria, especially the genus Streptomyces, have been shown to be potential biocontrol agents for phytopathogenic bacteria. Bacteria spot disease caused by Xanthomonas spp. may severely affect chili pepper (Capsicum annuum) crops with a subsequent decrease in productivity. Therefore, the objective of the study was to isolate rhizospheric actinobacteria from soil samples treated by physical methods and evaluate the inhibitory activity of the isolates over Xanthomonas. Initially, soil samples collected from avocado tree orchards were treated by dry heat air and microwave irradiation; thereafter, isolation was implemented. Then, antibacterial activity (AA) of isolates was evaluated by the double-layer agar method. Furthermore, the positive/negative effect on AA for selected isolates was evaluated on three culture media (potato-dextrose agar, PDA; yeast malt extract agar, YME; and oat agar, OA). Isolates were identified by 16S rRNA sequence analysis. A total of 198 isolates were obtained; 76 (series BVEZ) correspond to samples treated by dry heat and 122 strains (series BVEZMW) were isolated from samples irradiated with microwaves. A total of 19 dry heat and 25 microwave-irradiated isolates showed AA with inhibition zones (IZ, diameter in mm) ranging from 12.7 to 82.3 mm and from 11.4 to 55.4 mm, respectively. An increment for the AA was registered for isolates cultured on PDA and YME, with an IZ from 21.1 to 80.2 mm and 14.1 to 69.6 mm, respectively. A lower AA was detected when isolates were cultured on OA media (15.0 to 38.1 mm). Based on the 16S rRNA gene sequencing analysis, the actinobacteria belong to the Streptomyces (6) and Amycolatopsis (2) genera. Therefore, the study showed that microwave irradiation is a suitable method to increase the isolation of soil bacteria with AA against Xanthomonas sp. In addition, Streptomyces sp. BVEZ 50 was the isolate with the highest IZ (80.2 mm).

Halogenated Adenine and Adenosine Natural Products in Streptomyces sp. JCM9888

AbstractAscamycin 1 and dealanylascamycin 2 are adenosine containing nucleoside antibiotics carrying the rare 5’‐O‐sulfamoyl ribose motif and a chlorine atom attached to C2 of the adenine ring. Gene knockouts (ΔacmK and ΔacmJ) in the producing strain, Streptomyces sp. JCM9888, generated mutants that were disabled in the assembly of the sulfamoyl moiety. This resulted in the production of 2‐chloroadenosine 3 and 2‐chloroadenine 4, indicating that purine halogenation can occur independently of sulfamoylation. Incubations in media enriched in bromide content resulted also in the identification of 2‐bromoadenine 5, 2‐bromoadenosine 6 and 5′‐O‐sulfamoyl‐2‐bromoadenosine 7.

Light inducible gene expression system for Streptomyces

The LitR/CarH family comprises adenosyl B12-based photosensory transcriptional regulators that control light-inducible carotenoid production in nonphototrophic bacteria. In this study, we established a blue–green light-inducible hyperexpression system using LitR and its partner ECF-type sigma factor LitS in streptomycin-producing Streptomyces griseus NBRC 13350. The constructed multiple-copy number plasmid, pLit19, carried five genetic elements: pIJ101rep, the thiostrepton resistance gene, litR, litS, and σLitS-recognized light-inducible crtE promoter. Streptomyces griseus transformants harboring pLit19 exhibited a light-dependent hyper-production of intracellular reporter enzymes including catechol-2,3-dioxygenase and β-glucuronidase, extracellular secreted enzymes including laccase and transglutaminase, and secondary metabolites including melanin, flaviolin, and indigoidine. Cephamycin-producing Streptomyces sp. NBRC 13304, carrying an entire actinorhodin gene cluster, exhibited light-dependent actinorhodin production after the introduction of the pLit19 shuttle-type plasmid with the pathway-specific activator actII-ORF4. Insertion of sti fragment derived from Streptomyces phaeochromogenes pJV1 plasmid into pLit19 increased its light sensitivity, allowing gene expression under weak light irradiation. The two constructed Escherichia coli–Streptomyces shuttle-type pLit19 plasmids were found to have abilities similar to those of pLit19. We successfully established an optogenetically controlled hyperproduction system for S. griseus NBRC 13350 and Streptomyces sp. NBRC 13304.

Functional characterization and unraveling the structural determinants of novel steroid hydroxylase CYP154C7 from Streptomyces sp. PAMC26508

This study characterized cytochrome P450 enzyme CYP154C7 from Streptomyces sp. PAMC26508, emphasizing its capability to hydroxylate steroids, especially at the 16α-position. The enzymatic assay of CYP154C7 demonstrated effective conversion across a pH range of 7.2–7.6, with optimal activity at 30 °C in the Pdx/PdR plus NADH system. Kinetic analysis on most converted steroids (androstenedione and adrenosterone) was performed which shows a greater affinity for androstenedione (Km, 11.06 ± 1.903 μM; Vmax, 0.0062 ± 0.0002 sec−1) compared to adrenosterone (Km, 34.50 ± 6.2 μM; Vmax, 0.0119 ± 0.0007 sec−1). A whole-cell system in Escherichia coli, overexpressing recombinant CYP154C7, achieved substantial conversion for steroids, indicating that CYP154C7 can also be used as a potential whole-cell biocatalyst. To gain structural insights, homology models of CYP154C7 and its homologs were constructed using CYP154C5 (PDB ID: 6TO2), refined, validated, and used for docking studies. Comparative docking analysis suggests that lysine (K236) in the active site and tyrosine (Y197) in the substrate access channel of CYP154C7 are crucial for substrate selectivity and catalytic efficiency. This study suggests that CYP154C7 could be a promising candidate for developing modified steroids, providing valuable insights for protein engineering to design commercially useful CYP steroid hydroxylases with diverse substrate specificities.

In Silico evaluation of the anti-influenza potential of Streptomyces bioactive compounds

Influenza, a highly contagious respiratory viral disease characterized by its short incubation period and severe symptoms, is treatable with antiviral drugs targeting viremia. Among new antiviral agents, Actinobacteria, particularly from the Streptomyces genus, are notable for their ability to produce potent antiviral compounds. This study evaluates the antiviral potential of Streptomyces sp. KSF 103, isolated from Kuala Sat, Jerantut, Pahang, against the Influenza A virus (IAV). Using molecular docking tools such as AutoDock Vina and PyMOL, the interactions of four compounds – hypoxanthine, vitamin D, purine, and aminocaproic acid – were analyzed against IAV proteins. Vitamin D exhibited the highest binding affinity against H3N2’s M2 (−9.6 kcal/mol) and HA (−9.2 kcal/mol) proteins. Additionally, RMSD dynamics parameters indicated that the best-scoring complexes are predicted to be satisfactorily stable under physiological settings. These findings suggest that Streptomyces sp. KSF 103 could be a promising source for developing new antiviral treatments against influenza.

Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in Streptomyces albus J1074.

Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.