• Journal of Microbiology and Biotechnology
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• v.10 no.2
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• pp.176-180
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• 2000

Three polyene macrolide antibiotics including two new compounds were isolated from the culture mycelia of a Streptomyces species. The structures of these metabollites were determined as elizabethin, a previously reported 28-membered macrolide and two analohs, using combined spectroscopic methods. These compounds exhibited antifungal activity and cytotoxicity against a juman leukemia cell.

• Journal of Microbiology and Biotechnology
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• v.14 no.1
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• pp.212-215
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• 2004

In order to develop a biocontrol agent that can effectively control Fusarium wilt on Cymbidium genus, the effectiveness of antagonistic microbes against the cause pathogen was screened. The selected microbe showed a broad spectrum of antifungal activity, and the culture broth of this microbe had better preventive effect on Fusarium wilt than the commercial chemical agent in the pot assay. This isolated strain, GBA-12, was identified as Streptomyces kasugaensis, and the antifungal substance was purified from a broth culture of GBA-12. This purified substance was identified as a polyene macrolide (YS-822A) that was newly discovered from Streptomyces kasugaensis, and it exhibited antifungal activity against several phytopathogenic fungi.

• The Plant Pathology Journal
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• v.35 no.4
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• pp.341-350
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• 2019

Streptomyces padanus PMS-702 strain produces a polyene macrolide antibiotic fungichromin and displays antagonistic activities against many phytopathogenic fungi. In the present study, experimental formulations were assessed to improve the production of fungichromin, the efficacy of PMS-702 on the suppression of sporangial germination, and the reduction of cucumber downy mildew caused by Pseudoperonospora cubensis. PMS-702 strain cultured in a soybean meal-glucose (SMG) medium led to low levels of fungichromin accumulation and sporangial germination suppression. Increasing medium compositions and adding plant oils (noticeably coconut oil) in SMG significantly increased fungichromin production from 68 to $1,999.6{\mu}g/ml$. Microscopic examination reveals that the resultant suspensions significantly reduced sporangial germination and caused cytoplasmic aggregation. Greenhouse trials reveal that the application of PMS-702 cultural suspensions reduced downy mildew severity considerably. The addition of Tween 80 into the synthetic medium while culturing PMS-702 further increased the suppressive efficacy of downy mildew severity, particularly when applied at 24 h before inoculation or co-applied with inoculum. Fungichromin at $50{\mu}g/ml$ induced phytotoxicity showing minor necrosis surrounded with light yellowish halos on cucumber leaves. The concentration that leads to 90% inhibition (IC90) of sporangial germination was estimated to be around $10{\mu}g/ml$. The results provide a strong possibility of using the S. padanus PMS-702 strain as a biocontrol agent to control other plant pathogens.

• Microbiology and Biotechnology Letters
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• v.32 no.3
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• pp.238-242
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• 2004

Antifungal agents, flavofungin and fungichromin were isolated from the fermentation culture broth of a Streptomyces sp. SKM338. Biological evaluation of these antibiotics indicated that the compounds possesses broad spectrum antifungal activity against various pathogens. Especially, these compounds inhibited throughly growth of Didymella bryoniae, caused Gummy stem blight of melons, occurs in the southeastern Korea. Inhibition of this pathogen may be prevented from directly reducing both pre- and post-harvest yields.

• Journal of Microbiology and Biotechnology
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• v.24 no.9
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• pp.1226-1231
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• 2014

The rare actinomycete Pseudonocardia autotrophica was previously shown to produce a solubility-improved toxicity-reduced novel polyene compound named $\underline{N}ystatin$-like $\underline{P}seudonocardia$ $\underline{P}olyene$ (NPP). The low productivity of NPP in P. autotrophica implies that its biosynthetic pathway is tightly regulated. In this study, $wblA_{pau}$ was isolated and identified as a novel negative regulatory gene for NPP production in P. autotrophica, which showed approximately 49% amino acid identity with a global antibiotic down-regulatory gene, wblA, identified from various Streptomycetes species. Although no significant difference in NPP production was observed between P. autotrophica harboring empty vector and the S. coelicolor wblA under its native promoter, approximately 12% less NPP was produced in P. autotrophica expressing the wblA gene under the strong constitutive $ermE^*$ promoter. Furthermore, disruption of the $wblA_{pau}$ gene from P. autotrophica resulted in an approximately 80% increase in NPP productivity. These results strongly suggest that identification and inactivation of the global antibiotic down-regulatory gene wblA ortholog are a critical strategy for improving secondary metabolite overproduction in not only Streptomyces but also non-Streptomyces rare actinomycete species.

• KSBB Journal
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• v.22 no.4
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• pp.218-221
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• 2007

The polyene antifungal antibiotics, mostly produced by Gram-positive soil actinomycetes, are a family of type I polyketide macrolide ring compounds with 20$\sim$40 carbon backbone contain 3$\sim$8 conjugated double bonds. Using polyene-specific genomic screening strategy, we previously isolated three novel polyene-producing actinomycetes strains from soil, implying the potential application of these strains' spores as microbial pesticides. Here, we report that the sonication is a very efficient method for actinomycetes spore generation with a sonicator power-dependent manner. In addition, these sonication-driven actinomycetes spores retained significant portion of their cell viabilities as well as antifungal activities after freeze-drying procedure, implying the potential application of these strains' spores as microbial pesticides.

• Journal of Life Science
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• v.14 no.2
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• pp.225-228
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• 2004

Natamycin, produced by Streptomyces natalensis ATCC27448, is a polyene macrolide antibiotic, is widely used in the food industry in order to prevent mould contamination. This study carried out to develop an efficient purification process of natamycin from fermentation broth. The stability of natamycin in fermentation broth during storage period was investigated at 4$^{\circ}C$ and room temperature. After the storage of fermentation broth for 14 days at 4$^{\circ}C$, residual activity of natamycin was about 80% but decreased by 27% at room temperature. As solvent to extract natamycin from fermentation broth, methanol was the most efficient. A developed purification procedure includes methanol extraction and Diaion HP-20 column chromatography. Approximately 2.9 g of natamycin was obtained with a final yield of 69.1% and purity of 96.6% from 1.8 l of fermentation broth by this developed purification procedure.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.911-917
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• 2022

As valuable antibiotics, microbial natural products have been in use for decades in various fields. Among them are polyene compounds including nystatin, amphotericin, and nystatin-like Pseudonocardia polyenes (NPPs). Polyene macrolides are known to possess various biological effects, such as antifungal and antiviral activities. NPP A1, which is produced by Pseudonocardia autotrophica, contains a unique disaccharide moiety in the tetraene macrolide backbone. NPP B1, with a heptane structure and improved antifungal activity, was then developed via genetic manipulation of the NPP A1 biosynthetic gene cluster (BGC). Here, we generated a Streptomyces artificial chromosomal DNA library to isolate a large-sized NPP B1 BGC. The NPP B1 BGC was successfully isolated from P. autotrophica chromosome through the construction and screening of a bacterial artificial chromosome (BAC) library, even though the isolated 140-kb BAC clone (named pNPPB1s) lacked approximately 8 kb of the right-end portion of the NPP B1 BGC. The additional introduction of the pNPPB1s as well as co-expression of the 32-kb portion including the missing 8 kb led to a 7.3-fold increase in the production level of NPP B1 in P. autotrophica. The qRT-PCR confirmed that the transcription level of NPP B1 BGC was significantly increased in the P. autotrophica strain containing two copies of the NPP B1 BGCs. Interestingly, the NPP B1 exhibited a previously unidentified SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibition activity in vitro. These results suggest that the Streptomyces BAC cloning of a large-sized, natural product BGC is a valuable approach for titer improvement and biological activity screening of natural products in actinomycetes.

• Journal of Microbiology and Biotechnology
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• v.14 no.1
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• pp.121-127
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• 2004

Amphotericin B (AmB), an amphipathic polyene macrolide, is an antifungal drug produced by Streptomyces nodosus. Recently, AmB has been shown to exert antiviral activity against rubella virus and human immunodeficiency virus by different mechanisms. In this study, we evaluated the antiviral effect of AmB against Japanese encephalitis virus (JEV) and investigated which step of the viral life cycle was inhibited by AmB to understand the mechanism of antiviral action of AmB. AmB reduced both plaque size and number in the infected cells in a dose-dependent manner. In addition, a 200-fold reduction of infectious virus titer was observed by treatment of infected cells with $5\mug/ml$ of AmB. AmB acted at the post virus-infection step, but not during adsorption of virus to host cells. Western blot analysis revealed that the accumulated level of JEV envelope protein dramatically decreased in the infected cells by treatment with $5-10\mug/ml$ of AmB. Our results indicate that AmB inhibits the replication of JEV at the postinfection step by interfering with viral replication and/or by inhibiting the synthesis of viral proteins.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.756-760
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• 2005

Polyene macrolide amphotericin B (AmB) is the drug of choice for the treatment of disseminated fungal infections. However, because of its pronounced side effects, the drug has limited applicability. There are few interesting reports, which state that co-administration of the drug with homo-peptide of polyaspartic acid reduces the side effects of the drug. In our present study, an approach has been made to systematically synthesize low molecular weight heteropeptides consisting of L-aspartic acid and its derivative. It was hypothesized that such heteropeptides will reduce the toxic side effects of the drug by facile hydrophobic binding between the polymer and the drug. We have employed the strategy of solid phase peptide synthesis (SPPS) to synthesize low molecular weight hetero-peptides by using L-aspartic acid and benzyl-L-aspartic acid to induce the hydrophobic binding between the peptide and the drug. In future, the proposed methodology can be employed to tailor other polypeptides substituted with benzyl groups to reduce the nephrotoxicity of AmB.