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Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive 1 . The production of these antibacterial molecules reflects the relentless competition Streptomyces engage in with other bacteria, including other Streptomyces species 1 , 2 . Here we show that in addition to small-molecule antibiotics, Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryo-electron microscopy structure of these particles reveals an extended stalk topped by a ringed crown comprising the toxin repeats scaffolding five lectin-tipped spokes, which led us to name them umbrella particles. Streptomyces coelicolor encodes three umbrella particles with distinct toxin and lectin composition. Notably, supernatant containing these toxins specifically and potently inhibits the growth of select Streptomyces species from among a diverse collection of bacteria screened. For one target, Streptomyces griseus , inhibition relies on a single toxin and that intoxication manifests as rapid cessation of vegetative hyphal growth. Our data show that Streptomyces umbrella particles mediate competition among vegetative mycelia of related species, a function distinct from small-molecule antibiotics, which are produced at the onset of reproductive growth and act broadly 3 , 4 . Sequence analyses suggest that this role of umbrella particles extends beyond Streptomyces , as we identified umbrella loci in nearly 1,000 species across Actinobacteria. Streptomyces are discovered to produce antibacterial protein complexes that selectively inhibit the hyphal growth of related species, a function distinct from that of the small-molecule antibiotics they are known for.

The main aim of the current study is to explore the bioactive potential of Streptomyces sp. VITJS8 isolated from the marine saltern. The cultural, biochemical, and morphological studies were performed to acquire the characteristic features of the potent isolate VITJS8. The 16Sr DNA sequencing was performed to investigate the phylogenetic relationship between the Streptomyces genera. The structure of the compound was elucidated by gas chromatography-mass spectrometry (GC-MS), infra-red (IR), and ultra-violet (UV) spectroscopic data analysis. The GC-MS showed the retention time at 22.39 with a single peak indicating the purity of the active compound, and the molecular formula was established as C sub(14)H sub(9)ONCl sub(2 ) based on the peak at m/z 277 [M] super(+). Furthermore, separated by high-performance liquid chromatography (HPLC), their retention time (t sub(r)) 2.761 was observed with the absorption maxima at 310 nm. The active compound showed effective inhibitory potential against four clinical pathogens at 500 mu g/mL. The antioxidant activity was found effective at the IC sub(50) value of 500 mu g/mL with 90 % inhibition. The 3-(4,5-dimethylthiazol-2-yl)-2,5-ditetrazolium bromide (MTT) assay revealed the cytotoxicity against HepG2 cells at IC sub(50) of 250 mu g/mL. The progression of apoptosis was evidenced by morphological changes by nuclear staining. The DNA fragmentation pattern was observed at 250 mu g/mL concentration. Based on flow cytometric analysis, it was evident that the compound was effective in inhibiting the sub-G0/G1 phase of cell cycle. The in vitro findings were also supported by the binding mode molecular docking studies. The active compound revealed minimum binding energy of -7.84 and showed good affinity towards the active region of topoisomerase-2 alpha that could be considered as a suitable inhibitor. Lastly, we performed 30 ns molecular dynamic simulation analysis using GROMACS to aid in better designing of anticancer drugs. Simulation result of root mean square deviation (RMSD) analysis showed that protein-ligand complex reaches equilibration state around 10 ns that illustrates the docked complex is stable. We propose the possible mechanism of sesquiterpenes to play a significant role in antitumor cascade. Hence, our studies open up a new facet for a potent drug as an anticancer agent.

In this study, metabolites involved in the free-biomass filtrates for three endophytic actinomycetes of Streptomyces capillispiralis Ca-1, Streptomyces zaomyceticus Oc-5, and Streptomyces pseudogriseolus Acv-11 were used as biocatalysts for green synthesis of silver nanoparticles (Ag-NPs). Characterization of biosynthesized Ag-NPs was accomplished using UV-Vis spectroscopy, X-ray diffraction patterns (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM-EDX), transmission electron microscopy (TEM), and particle size analyzer. The biosynthesized Ag-NPs showed maximum surface plasmon resonance (SPR) at 440 for strain Ca-1 and 450 for both strains of OC-5 and Acv-11. Nanoparticle spherical shape was recorded with size ranging from 23.77 to 63.14 nm, 11.32 to 36.72 nm, and 11.70 to 44.73 nm for Ca-1, Oc-5, and Acv-11, respectively. SEM-EDX analysis exhibited the weight percentages of 17.3, 22.3, and 48.7% for Ag-NPs synthesized by strains Ca-1, Oc-5 and Acv-11, respectively. The activities of biosynthesized Ag-NPs were concentration dependent and the obtained results confirmed the efficacy of Ag-NPs as antimicrobial agents against Gram-positive and Gram-negative bacteria as well unicellular and multicellular fungi. The MIC for Gram-positive bacteria, Gram-negative bacteria ( E. coli ), and eukaryotic microorganisms was 0.25 mM with clear zone ranging from 10.3 to 14.6 mm, while MIC for Pseudomonas aeruginosa was 1.0 mM for Ag-NPs synthesized by strain Ca-1 and 0.25 mM for those synthesized by strains Oc-5 and Acv-11. Moreover, Ag-NPs exhibited antimicrobial activity against four plant pathogenic fungi represented by Alternaria alternata , Fusarium oxysporum , Pythium ultimum , and Aspergillus niger at 2.0, 1.5, 1.0, and 0.5 mM of Ag-NPs with different degree. In vitro assessment of the antioxidant efficacy of biosynthesized Ag-NPs was achieved by scavenging assay of H 2 O 2 , reducing power of Fe 3+ , or total antioxidant assay. The results showed that antioxidant activities of Ag-NPs were concentration dependent with the highest activity at Ag-NP concentration of 2.0 mM. Furthermore, the biosynthesized NPs have prospective bioinsecticidal activity against Culex pipiens and Musca domestica. Green synthesis of NPs could be quite potential for the development of new bioactive compounds used in different biomedical applications.

Application of actinobacteria has grown exponentially in recent years in sustainable agricultural. Most actinobacterial inoculants are tailored to function as either biocontrol agents or biofertilizers. Hence, there is the need to obtain and include multifunctional actinobacterial strains in inocula formulations. In this research, 90 actinobacterial isolates were isolated from rhizospheric and non-rhizospheric soils of Algerian Saharan arid regions and were screened for their activity against the phytopathogenic fungi Alternaria alternata, Aspergillus flavus, Botrytis cinerea, Fusarium oxysporum, and Fusarium solani. Five isolates that inhibited at least three of these fungi were characterized according to morphological, environmental and biochemical parameters, and were preliminarily identified as Streptomyces enissocaesilis A1, Streptomyces olivoverticillatus A5, Streptomyces erumpens A6, Streptomyces cavourensis A8, and Streptomyces microflavus A20. These strains were then screened for plant growth promoting activities. All strains produced siderophores, hydrocyanic acid, ammonia and the auxin indole-3-acetic acid (IAA) and were capable of solubilizing phosphate. The highest producer of siderophores (69.19 percent siderophore units), ammonia (70.56 μg mL−1) and IAA (148.76 μg mL−1) was strain A8, A20, and A5, respectively. These findings showed that the five actinobacteria are multipurpose strains with simultaneous antifungal and plant growth promoting activities and have the potential to be used for sustainable agricultural practices, particularly in arid regions.

Streptomyces albusJ1074 is a streptomycete strain widely used as a host for expression of secondary metabolite gene clusters. Bioinformatic analysis of the genome of this organism predicts the presence of 27 gene clusters for secondary metabolites. We have used three different strategies for the activation of some of these silent/cryptic gene clusters in S.albusJ1074: two hybrid polyketide-non-ribosomal peptides (PK-NRP) (antimycin and 6-epi-alteramides), a type I PK (candicidin), a non-ribosomal peptides (NRP) (indigoidine) and glycosylated compounds (paulomycins). By insertion of a strong and constitutive promoter in front of selected genes of two clusters, production of the blue pigment indigoidine and of two novel members of the polycyclic tetramate macrolactam family (6-epi-alteramides A and B) was activated. Overexpression of positive regulatory genes from the same organism also activated the biosynthesis of 6-epi-alteramides and heterologous expression of the regulatory gene pimM of the pimaricin cluster activated the simultaneous production of candicidins and antimycins, suggesting some kind of cross-regulation between both clusters. A cluster for glycosylated compounds (paulomycins) was also identified by comparison of the high-performance liquid chromatography profiles of the wild-type strain with that of a mutant in which two key enzymes of the cluster were simultaneously deleted. Streptomyces albus J1074 genome mining predicts the presence of twenty seven gene clusters for secondary metabolites. The products generated by five of them have been identified using different. These include two hybrid polyketide-non ribosomal peptides (PK-NRP) (antimycin and 6-epi-alteramides), a type I PK (candicidin), a NRP (indigoidine) and glycosylated compounds (paulomycins).

Abstract Despite their importance in the chemical industry, the significance of rare earths in biology has been largely overlooked. Here, it is reported that the rare earth, scandium (Sc), causes antibiotic overproduction by 2–25-fold when added at a low concentration (10–100 µM) to cultures of Streptomyces coelicolor A3(2) (actinorhodin producer), Streptomyces antibioticus (actinomycin producer), and Streptomyces griseus (streptomycin producer). Not just for enhancement of antibiotic production, scandium was also effective in activating the dormant ability to produce actinorhodin in Streptomyces lividans. The effects of scandium were exerted at the level of transcription of pathway-specific positive regulatory genes, as demonstrated by marked up-regulation of actII-ORF4 in S. coelicolor cells exposed to this element. The bacterial alarmone, guanosine 5′-diphosphate 3′-diphosphate, was essential for actinorhodin overproduction provoked by scandium.

Two novel actinomycetes, designated strains 2C-SSA16(2) T and 1C-GS8 T , were isolated from the cuticle of Camponotus japonicus Mayr, collected from Northeast Agricultural University, Heilongjiang Province, north China. Both of them contained genes (involved in antibiotics biosynthesis) of the ketosynthase (KS) and methyl malonyl transferase domains (PKS-I) and the adenylation domain (NRPS). A polyphasic study was carried out to establish the taxonomic positions of these strains. The 16S rRNA gene sequence analysis showed that the two novel isolates 2C-SSA16(2) T and 1C-GS8 T exhibited 98.8% similarity with each other and that they are most closely related to Streptomyces umbrinus JCM 4521 T (99.0, 98.6%), Streptomyces ederensis JCM 4958 T (98.9, 98.7%), Streptomyces aurantiacus JCM 4453 T (98.6, 98.2%), Streptomyces glomeroaurantiacus JCM 4677 T (98.6, 98.1%), Streptomyces tauricus JCM4837 T (98.2, 98.0%) and Streptomyces phaeochromogenes JCM 4070 T (98.2, 99.2%). The corresponding phylogenetic analysis based on partial gyr B gene sequences showed that strains 2C-SSA16(2) T and 1C-GS8 T formed a cluster with the above-mentioned strains. The DNA–DNA hybridization data and phenotypic characteristics indicated that strains 2C-SSA16(2) T and 1C-GS8 T could be readily distinguished from each other and their closest phylogenetic relatives. Therefore, these two strains are suggested to represent two novel species of the genus Streptomyces , for which the names Streptomyces camponoti sp. nov. and Streptomyces cuticulae sp. nov. are proposed. The type strains are 2C-SSA16(2) T (=CGMCC 4.7276 T  = DSM 100522 T ) and 1C-GS8 T (=CGMCC 4.7348 = DSM 103127 T ), respectively.

The roles of many sigma factors are unclear in regulatory mechanism of secondary metabolism in Streptomyces. Here, we report the regulation network of a group 3 sigma factor, WhiG sub(ch), from a natamycin industrial strain Streptomyces chattanoogensis L10. WhiG sub(ch) regulates the growth and morphological differentiation of S. chattanoogensis L10. The whiG sub(ch) deletion mutant decreased natamycin production by about 30 % and delayed natamycin production more than 24 h by delaying the growth. Overexpression of the whiG sub(ch) gene increased natamycin production in large scale production medium by about 26 %. WhiG sub(ch) upregulated the transcription of natamycin biosynthetic gene cluster and inhibited the expression of migrastatin and jadomycin analog biosynthetic polyketide synthase genes. WhiG sub(ch) positively regulated natamycin biosynthetic gene cluster by directly binding to the promoters of scnC and scnD, which were involved in natamycin biosynthesis, and these binding sites adjacent to translation start codon were determined. Thus, this paper further elucidates the high natamycin yield mechanisms of industrial strains and demonstrates that a valuable improvement in the yield of the target metabolites can be achieved through manipulating the transcription regulators.

Background Streptomyces is renowned for its robust biosynthetic capacity in producing medically relevant natural products. However, the majority of natural products biosynthetic gene clusters (BGCs) either yield low amounts of natural products or remain cryptic under standard laboratory conditions. Various heterologous production hosts have been engineered to address these challenges, and yet the successful activation of BGCs has still been limited. In our search for a valuable addition to the heterologous host panel, we identified the strain Streptomyces sp. A4420, which exhibited rapid initial growth and a high metabolic capacity, prompting further exploration of its potential. Results We engineered a polyketide-focused chassis strain based on Streptomyces sp. A4420 (CH strain) by deleting 9 native polyketide BGCs. The resulting metabolically simplified organism exhibited consistent sporulation and growth, surpassing the performance of most existing Streptomyces based chassis strains in standard liquid growth media. Four distinct polyketide BGCs were chosen and expressed in various heterologous hosts, including the Streptomyces sp. A4420 wild-type and CH strains, alongside Streptomyces coelicolor M1152, Streptomyces lividans TK24, Streptomyces albus J1074, and Streptomyces venezuelae NRRL B-65442. Remarkably, only the Streptomyces sp. A4420 CH strain demonstrated the capability to produce all metabolites under every condition outperforming its parental strain and other tested organisms. To enhance visualization and comparison of the tested strains, we developed a matrix-like analysis involving 15 parameters. This comprehensive analysis unequivocally illustrated the significant potential of the new strain to become a popular heterologous host. Conclusion Our engineered Streptomyces sp. A4420 CH strain exhibits promising attributes for the heterologous expression of natural products with a focus on polyketides, offering an alternative choice in the arsenal of heterologous production strains. As genomics and cloning strategies progress, establishment of a diverse panel of heterologous production hosts will be crucial for expediting the discovery and production of medically relevant natural products derived from Streptomyces .

ET received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 720793 TOPCAPI—thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients. SY was funded from H2020 TOPCAPI. HZ received funding from the US National Institutes of Health (NIH) under Award No. AI144967.