Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712.
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Accepted version
Embargoed until: 2099-01-01
Reason: Not yet published.
Embargoed until: 2099-01-01
Reason: Not yet published.
Pagination
e202400357 - ?
DOI
10.1002/cbic.202400357
Journal
Chembiochem
Metadata
Show full item recordAbstract
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.
Authors
Lai, H-E; Kennedy, A; Tanner, L; Bartram, E; Chee, SM; Freemont, P; Moore, SCollections
- Biochemistry [23]