Abstract
From the wild-type strain Steptomyces sp. AK 671, three nitrogen-containing octaketides were isolated, bhimamycins F, H and I, besides the known azaanthraquinone utahmycin A and polyketide shunt products SEK 4, SEK 4b, mutactin, dehydromutactin and EM18. The structures were characterized by MS and NMR experiments. The hitherto unknown absolute configuration of the two enantiomers of EM18 was determined by online-CD spectroscopy and quantum-chemical CD calculations. Bhimamycins H and I show weak antibacterial activities, whereas the enzyme phosphodiesterase 4 is strongly inhibited by bhimamycins H and I, which has never been reported for nitrogen-containing octaketides. In addition, bhimamycin H inhibits the enzyme glycogen synthase kinase-3β.
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Acknowledgements
We are grateful to Prof M Goodfellow, Newcastle University, for providing us the strain Streptomyces sp. AK 671. Financial support from the DFG (German Research Association, Sonderforschungsbereich 630 “Agents against Infectious Diseases”, Universiät Würzburg) and from the Ministry of Science, Economic affairs and Transport of Schleswig-Holstein, Kiel, of the project no. 12208009 “Aufbau einer Reinsubstanz-Bibliothek mariner Naturstoffe’ is gratefully acknowledged. We thank E Ruckdeschel and Dr M Grüne for the NMR experiments, F Dadrich and Dr M Büchner for the mass spectra, and F Witterauf for the measurement of the online-CD spectra (Universität Würzburg). JFI and JW are grateful to A Erhard (Kieler Wirkstoff-Zentrum) for performing the activity tests. PJ and HPF thank A Kulik (Universität Tübingen) for assistance in fermentations and HPLC-ESI-MS analysis.
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Art. No. 67 in ‘Biosynthetic Capacities of Actinomycetes’. Art. No. 66: see Helaly et al.
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Jetter, P., Steinert, C., Knauer, M. et al. New bhimamycins from Streptomyces sp. AK 671. J Antibiot 66, 719–726 (2013). https://doi.org/10.1038/ja.2013.82
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DOI: https://doi.org/10.1038/ja.2013.82
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