Abstract
Expression of the aranciamycin biosynthetic gene cluster in Streptomyces diastatochromogenes Tü6028 resulted in production of four novel compounds, aranciamycins E, F, G, and H with different decorations in the tetracyclic backbone. Two derivatives contain a d-amicetose moiety at C7 (aranciamycins F and G), two are hydroxylated at position C1 (aranciamycins E and G), and one is hydroxylated at C13 (aranciamycin F). Analysis of the biological activities of the aranciamycins against two human tumor cell lines—MCF-7 and MATU—shows surprising impact of the hydroxyl group at position C1 on activity. As aranciamycins E and G were the most active derivatives, hydroxylation of the C1 appears to coincide with increased antitumor activity of aranciamycins.
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Aknowledgment
This work was supported in part by the BMBF (GenoMic-Plus) and by the DFG (Synthese von Dekaketid-Zwischenstufen der Polyketidsynthasen vom TypII), both grants to AB.
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Figure S1
NMR spectra of the aranciamycin H molecule (DOC 65.5 kb)
Figure S2
NMR spectra of the aranciamycin G molecule. (DOC 114 kb)
Figure S3
NMR spectra of the aranciamycin F molecule. (DOC 89.0 kb)
Figure S4
NMR spectra of the aranciamycin E molecule. (DOC 82.0 kb)
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Luzhetskyy, A., Hoffmann, J., Pelzer, S. et al. Aranciamycin analogs generated by combinatorial biosynthesis show improved antitumor activity. Appl Microbiol Biotechnol 80, 15–19 (2008). https://doi.org/10.1007/s00253-008-1515-1
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DOI: https://doi.org/10.1007/s00253-008-1515-1