Biosynthesized selenium nanoparticles (SeNPs) have attracted much attention because of their unique physical, chemical, and biological properties. The microbial reduction of selenium salts to SeNPs has great potential, while there is a lack of elite strains. In this study, we explored the reduction of Na₂SeO₃ by Streptomyces avermitilis into SeNPs. The colonies and hyphae of the strain and the synthesized SeNPs were characterized by optical microscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). At the same time, the inhibitory activity of SeNPs on Fusarium oxysporum, the main pathogen causing root rot of Lycium barbarum, was studied. The results showed that S. avermitilis converted Na₂SeO₃ into SeNPs and tolerated 300 mmol/L Na₂SeO₃, demonstrating strong tolerance. S. avermitilis synthesized spherical SeNPs in the cytoplasm, and most of SeNPs had a diameter of about 100 nm and were released by hyphal fracture. The SeNPs synthesized by S. avermitilis were amorphous, and their surfaces were dominated by C and Se, with the existence of O, N and other elements. SeNPs had functional groups such as -OH, C=O, C-N, and C-H, which were closely related to the stability and biological activity of SeNPs. The SeNPs synthesized by S. avermitilis showcased significant inhibitory activity on F. oxysporum, and 25.0 μmol/mL SeNPs showcased the inhibition rate of 77.61% and EC₅₀ of 0.556 μmol/mL. In conclusion, S. avermitilis can tolerate high Na₂SeO₃ stress and mediate the synthesis of SeNPs. The synthesized SeNPs have good stability and strong inhibitory activity, demonstrating the potential application value in the preparation of SeNPs and the control of L. barbarum root rot.
Streptomyces/metabolism* ; Fusarium/drug effects* ; Lycium/microbiology* ; Selenium/metabolism* ; Nanoparticles/chemistry* ; Plant Diseases/microbiology* ; Metal Nanoparticles/chemistry* ; Antifungal Agents/pharmacology*

In recent years, potato scab caused by pathogenic Streptomyces spp. has become widespread globally, with increasing damage severely compromising the commercial value and storability of tubers. The pathogens are transmitted through the soil and seeds of potato, while existing control technologies have demonstrated limited efficacy in preventing the colonization and spread of pathogens, which pose a critical bottleneck in the sustainable development of the potato industry. This study systematically examines the pathogen characteristics and pathogenic mechanisms, evaluates the impacts of soil nutrients and microbial community structure on disease severity, and analyzes limitations in current chemical control, biological control, and disease-resistant variety breeding approaches. We propose an integrated control strategy of disease-resistant varieties, phosphorus fertilizer reduction, fertilizer efficiency enhancement, and phosphorus-soluble antagonistic fungicides, aiming to provide novel research perspectives for achieving effective prevention and control of potato scab.
Solanum tuberosum/microbiology* ; Plant Diseases/prevention & control* ; Streptomyces/pathogenicity* ; Disease Resistance ; Fungicides, Industrial/pharmacology* ; Fertilizers ; Soil Microbiology

In recent years, potato scab caused by Streptomyces scabies is aggravating year by year, becoming an industrial problem urgently to be resolved. Screening antagonistic bacteria with good inhibitory effect and wide adaptability is the main measure to realize effective prevention and control of the disease. This study screened three strains of antagonistic bacteria DXT2-4, T2-1 and 21-14 with good inhibitory effect on S. scabies by using plate standoff test, and identified them as Bacillus altitudinis, Bacillus safensis and Bacillus pumilus, respectively, based on morphological characteristics, physiological and biochemical properties, and 16S rRNA gene sequences. DXT2-4, T2-1 and 21-14 showed the pot control efficacy of 68.83%, 48.57%, and 57.14%, respectively. The field control efficacy of the three strains was 59.48%, 34.58% and 51.75% in Hulun Buir, Inner Mongolia Autonomous Region and 55.14%, 36.05%, and 49.05% in Huizhou, Guangdong. The three strains could grow normally in the media with pH 1.0-13.0 and with 1%-11% NaCl, and they had inhibitory effects on Rhizoctonia solani, Verticillium dahliae, Alternaria solani, and Fusarium oxysporum. The indole-3-acetic acid yields of DXT2-4, T2-1, and 21-14 were 2.23, 1.11, and 1.67 mg/L, respectively. DXT2-4 and 21-14 demonstrated strong abilities to solubilize phosphorus. The optimal carbon source, nitrogen source, and inorganic salt for fermentation of strain DXT2-4 were 2% molasses+2% corn starch, 2% soybean meal, and 0.3% MgSO₄·7H₂O, respectively. These findings suggest the three strains of bacteria can efficiently inhibit the growth of S. scabies and have strong environmental adaptability. Particularly, DXT2-4 has the best effects of inhibiting the disease and promoting plant growth, showing a high development value and broad application prospects, this is of great significance for promoting sustainable potato production and ensuring the environmentally sound utilization of resources.
Streptomyces/metabolism* ; Fermentation ; Plant Diseases/prevention & control* ; Solanum tuberosum/growth & development* ; Bacillus/growth & development* ; Antibiosis

Lysobacter harbors a plethora of cryptic biosynthetic gene clusters (BGCs), albeit only a limited number have been analyzed to date. In this study, we described the activation of a cryptic polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) gene cluster (lsh) in Lysobacter sp. DSM 3655 through promoter engineering and heterologous expression in Streptomyces sp. S001. As a result of this methodology, we were able to isolate two novel linear lipopeptides, lysohexaenetides A (1) and B (2), from the recombinant strain S001-lsh. Furthermore, we proposed the biosynthetic pathway for lysohexaenetides and identified LshA as another example of entirely iterative bacterial PKSs. This study highlights the potential of heterologous expression systems in uncovering cryptic biosynthetic pathways in Lysobacter genomes, particularly in the absence of genetic manipulation tools.
Lysobacter/metabolism* ; Streptomyces/metabolism* ; Lipopeptides/metabolism* ; Polyketide Synthases/genetics* ; Multigene Family

Natural cyclohexapeptide AFN A₁ fromStreptomyces alboflavus 313 has moderate antibacterial and antitumor activities. An artificial designed AFN A₁ homodimer, di-AFN A₁, is an antibiotic exhibiting 10 to 150 fold higher biological activities, compared with the monomer. Unfortunately, the yield of di-AFN A₁ is very low (0.09 ± 0.03 mg·L^-1) in the engineered strain Streptomyces alboflavus 313_hmtS (S. albo/313_hmtS), which is not friendly to be genetically engineered for titer improvement of di-AFN A₁ production. In this study, we constructed a biosynthetic gene cluster for di-AFN A₁ and increased its production through heterologous expression. During the collection of di-AFN A₁ biosynthetic genes, the afn genes were located at three sites of S. alboflavus 313 genome. The di-AFN A₁ biosynthetic gene cluster (BGC) was first assembled on one plasmid and introduced into the model strain Streptomyces lividans TK24, which produced di-AFN A₁ at a titer of 0.43 ± 0.01 mg·L^-1. To further increase the yield of di-AFN A₁, the di-AFN A₁ BGC was multiplied and split to mimic the natural afn biosynthetic genes, and the production of di-AFN A₁ increased to 0.62 ± 0.11 mg·L^-1 in S. lividans TK24 by the later strategy. Finally, different Streptomyces hosts were tested and the titer of di-AFN A₁ increased to 0.81 ± 0.17 mg·L^-1, about 8.0-fold higher than that in S. albo/313_hmtS. Successful heterologous expression of di-AFN A₁ with a remarkable increased titer will greatly facilitate the following synthetic biological study and drug development of this dimeric cyclohexapeptide.
Cloning, Molecular ; Streptomyces/metabolism* ; Multigene Family ; Anti-Bacterial Agents/metabolism* ; Plasmids/genetics*

OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ² = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.
Adenosine Diphosphate/pharmacology* ; Adenosine Triphosphate ; Animals ; Molluscacides/pharmacology* ; Silica Gel/pharmacology* ; Snails ; Streptomyces ; Water

Natamycin is a safe and efficient antimycotics which is widely used in food and medicine industry. The polyene macrolide compound, produced by several bacterial species of the genus Streptomyces, is synthesized by type Ⅰ polyketide synthases using acetyl-CoA, malonyl-CoA, and methylmalonyl-CoA as substrates. In this study, four pathways potentially responsible for the supply of the three precursors were evaluated to identify the effective precursor supply pathway which can support the overproduction of natamycin in Streptomyces gilvosporeus, a natamycin-producing wild-type strain. The results showed that over-expressing acetyl-CoA synthetase and methylmalonyl-CoA mutase increased the yield of natamycin by 44.19% and 20.51%, respectively, compared with the wild type strain under shake flask fermentation. Moreover, the yield of natamycin was increased by 66.29% compared with the wild-type strain by co-overexpression of acetyl-CoA synthetase and methylmalonyl-CoA mutase. The above findings will facilitate natamycin strain improvement as well as development of strains for producing other polyketide compounds.
Natamycin/metabolism* ; Methylmalonyl-CoA Mutase/metabolism* ; Acetyl Coenzyme A/metabolism* ; Streptomyces/genetics* ; Polyketide Synthases/metabolism*

Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.
Antifungal Agents/pharmacology* ; Fungi ; Natamycin ; Streptomyces

Carrimycin (CAM) is a new antibiotics with isovalerylspiramycins (ISP) as its major components. It is produced by Streptomyces spiramyceticus integrated with a heterogenous 4″-O-isovaleryltransferase gene (ist). However, the present CAM producing strain carries two resistant gene markers, which makes it difficult for further genetic manipulation. In addition, isovalerylation of spiramycin (SP) could be of low efficiency as the ist gene is located far from the SP biosynthesis gene cluster. In this study, ist and its positive regulatory gene acyB2 were inserted into the downstream of orf54 gene neighboring to SP biosynthetic gene cluster in Streptomyces spiramyceticus 1941 by using the CRISPR-Cas9 technique. Two new markerless CAM producing strains, 54IA-1 and 54IA-2, were obtained from the homologous recombination and plasmid drop-out. Interestingly, the yield of ISP in strain 54IA-2 was much higher than that in strain 54IA-1. Quantitative real-time PCR assay showed that the ist, acyB2 and some genes associated with SP biosynthesis exhibited higher expression levels in strain 54IA-2. Subsequently, strain 54IA-2 was subjected to rifampicin (RFP) resistance selection for obtaining high-yield CAM mutants by ribosome engineering. The yield of ISP in mutants resistant to 40 μg/mL RFP increased significantly, with the highest up to 842.9 μg/mL, which was about 6 times higher than that of strain 54IA-2. Analysis of the sequences of the rpoB gene of these 7 mutants revealed that the serine at position 576 was mutated to alanine existed in each sequenced mutant. Among the mutants carrying other missense mutations, strain RFP40-6-8 which carries a mutation of glutamine (424) to leucine showed the highest yield of ISP. In conclusion, two markerless novel CAM producing strains, 54IA-1 and 54IA-2, were successfully developed by using CRISPR-Cas9 technique. Furthermore, a novel CAM high-yielding strain RFP40-6-8 was obtained through ribosome engineering. This study thus demonstrated a useful combinatory approach for improving the production of CAM.
CRISPR-Cas Systems/genetics* ; Genetic Engineering ; Ribosomes ; Spiramycin ; Streptomyces/genetics*

Streptomyces are major sources of bioactive natural products. Genome sequencing reveals that Streptomyces have great biosynthetic potential, with an average of 20-40 biosynthetic gene clusters each strain. However, most natural products from Streptomyces are produced in low yields under regular laboratory cultivation conditions, which hamper their further study and drug development. The production of natural products in Streptomyces is controlled by the intricate regulation mechanisms. Manipulation of the regulatory systems that govern secondary metabolite production will strongly facilitate the discovery and development of natural products of Streptomyces origin. In this review, we summarize progresses in pathway-specific regulators from Streptomyces in the last five years and highlight their role in improving the yields of corresponding natural products.
Biological Products ; Multigene Family ; Secondary Metabolism ; Streptomyces/genetics*