Nanaomycin H: A new nanaomycin analog

Nakashima, Takuji; Kimura, Tōru; Miyano, Rei; Matsuo, Hirotaka; Hirose, Tomoyasu; Kimishima, Aoi; Nonaka, Kenichi; Iwatsuki, Masato; Nakanishi, Jun; Takahashi, Yōko; Ōmura, Satoshi

doi:10.1016/j.jbiosc.2017.01.011

Cited by 15 publications

(19 citation statements)

References 11 publications

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“…Our earlier studies demonstrated that pyrizomicin A showed antimicrobial activity, 24 whereas nanaomycin H did not express any notable antimicrobial activity. 25 In agreement with previous findings, an application of pyrizomicin A at 50 μg/mL completely killed MDCK cells (Fig. 3A).…”

Section: Resultssupporting

confidence: 93%

“…Recombinant human transforming growth factor-β1 (TGF-β1) was purchased from Funakoshi (Tokyo, Japan). Pyrizomicin A 24 and Nanaomycin H 25 were isolated from a culture broth of Streptomyces rosa subsp. notoensis OS-3966 and Lechevalieria aerocolonigenes K10-0216, respectively, by physicochemical screening.…”

Section: Reagents Chemicals and Photoactivatable Substratesmentioning

confidence: 99%

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An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors

et al. 2018

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Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to celladhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

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Section: Resultssupporting

confidence: 93%

Section: Reagents Chemicals and Photoactivatable Substratesmentioning

confidence: 99%

An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors

et al. 2018

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“…With respect to the three entries in question, the name of the original compound and retention period by lyophilization are stated, all three having been stored for 35 years or more. The compounds recently discovered, namely bisoxazolomycin [ 32 ], the iminimycins [ 33 , 34 ], and the nanaomycins [ 35 , 36 ], would probably not have been detected by an assay system seeking a specific bioactive property, the compounds being found as a direct result of PC screening. Discovery of the iminimycins and nanaomycins are described in detail below in Section 4.2 .…”

Section: Novel Compounds Discovered By Physicochemical (Pc) Screenmentioning

confidence: 99%

“…The second, which we named nanaomycin G ( Figure 2 c) [ 35 ], has a unique 1-indanone skeleton fused with a tetrahydropyran ring. During chromatographic purification of these compounds, another new compound was obtained, nanaomycin H ( Figure 2 c) [ 36 ]. Structure elucidation of nanaomycin H showed it to be a pyranonaphthoquinone with a mycothiol moiety.…”

Section: Novel Compounds Discovered From the Kitasato Microbial LImentioning

confidence: 99%

“…These compounds would not have been found using an assay simply targeting bioactivity. Incidentally, the production medium of nanaomycin A to E is mainly composed of glycerol and soybean meal [ 53 ], whereas nanaomycins F, G, and H were produced on a medium containing mainly soluble starch and defatted wheat germ [ 35 , 36 ]. This raises the interesting possibility that simply changing the composition of culture media may allow the discovery of new compounds.…”

Section: Novel Compounds Discovered From the Kitasato Microbial LImentioning

confidence: 99%

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Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics

2018

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Global public health faces a desperate situation, due to the lack of effective antibiotics. Coordinated steps need to be taken, worldwide, to rectify this situation and protect the advances in modern medicine made over the last 100 years. Work at Japan’s Kitasato Institute has been in the vanguard of many such advances, and work is being proactively tailored to promote the discovery of urgently needed antimicrobials. Efforts are being concentrated on actinomycetes, the proven source of most modern antibiotics. We devised a novel physicochemical screening mechanism, whereby simple physico-chemical properties, in conjunction with related detection methods, such as LC/MS, LC/UV, and polarity, could be used to identify or predict new compounds in a culture broth, simply by comparing results with existing databases. New compounds are isolated, purified, and their structure determined before being tested for any bioactivity. We used lyophilized actinomycete strains from the Kitasato Microbial Library, most more than 35 years old, and found 330 strains were producers of useful bioactive substances. We also tested organisms found in fresh samples collected in the complex environments from around plant roots, as well as from sediments of mangrove forests and oceans, resulting in the discovery of 36 novel compounds from 11 actinomycete strains. A compound, designated iminimycin, containing an iminium ion in the structure was discovered from the culture broth of Streptomyces griseus OS-3601, which had been stored for a long time as a streptomycin-producing strain. This represented the first iminium ion discovery in actinomycetes. Compounds with a cyclopentadecane skeleton containing 5,6-dihydro-4-hydroxyl-2-pyrone ring and tetrahydrofuran ring, designated mangromicins, were isolated from the culture broth of Lechevalieria aerocolonigenes K10-0216 obtained from sediment in a mangrove forest. These structures are extremely unique among natural compounds. From the same culture broth, new steroid compounds, named K10-0216 KA and KB, and other new compounds having a thiazole and a pyridine ring, named pyrizomicin A and B, were discovered. New substances can be found from actinomycetes that have been exhaustively studied. Novel compounds with different skeletons can be found from a single broth of one strain. The sought after new antibiotics will arise from continued exploitation of the actinomycetes, especially rare actinomycetes. Work on new organisms and samples should be augmented by re-examination of known actinomycetes already in storage. New research should also be carried out on the manipulation of culture media, thereby stimulating actinomycete strains to produce novel chemicals. The establishment of wide-ranging international research collaborations will facilitate and expedite the efficient and timely discovery and provision of bioactive compounds to help maintain and promote advances in global public health.

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