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bioRxiv · 10.1101/2024.04.17.589956

Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712

Lai, H.-E.·Tanner, L.·Kennedy, A.·Chee, S. M.·Freemont, P.·Moore, S.
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Abstract

Indolocarbazoles are natural products with a broad spectrum of reported bioactivities. A distinct feature of indolocarbazole biosynthesis is the modification of the indole and maleimide rings by regioselective tailoring enzymes. Here, we study a new indolocarbazole variant, which is encoded by the acfXODCP genes from Streptomyces venezuelae ATCC 10712. First, we characterise this pathway by expressing the acfXODCP genes in Streptomyces coelicolor, which led to the production of a C-5/C-5-dihydroxylated indolocarbazole. We name this new product arcyriaflavin F. Second, we demonstrate the flavin-dependent monooxygenase AcfX catalyses the C-5/C-5 dihydroxylation of the unsubstituted arcyriaflavin A into arcyriaflavin F. Interestingly, AcfX shares homology to EspX from erdasporine A biosynthesis, which instead catalyses a single C-6 indolocarbazole hydroxylation. In summary, we report a new indolocarbazole biosynthetic pathway and a regioselective C-5 indole ring tailoring enzyme AcfX. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=46 SRC="FIGDIR/small/589956v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@c0c397org.highwire.dtl.DTLVardef@16915dforg.highwire.dtl.DTLVardef@1ae538org.highwire.dtl.DTLVardef@1bef4ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Lai, H.-E., Tanner, L., Kennedy, A., Chee, S. M., Freemont, P., Moore, S.. 2024-04-20. Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712. https://doi.org/10.1101/2024.04.17.589956

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