Biosynthesis of Arcyriaflavin F from Streptomyces venezuelaeATCC 10712

Indolocarbazoles are natural products with broad 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 Stre...

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Published in:Chembiochem : a European journal of chemical biology 2024-07
Main Authors: Lai, Hung-En, Kennedy, Agata, Tanner, Lewis, Bartram, Emma, Chee, Soo Mei, Freemont, Paul, Moore, Simon
Format: Article
Language:English
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Summary:Indolocarbazoles are natural products with broad 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 assign as a 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.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.202400357