Recursor-directed biosynthesis of unnatural novel prenylated alkaloids by exploring indole prenyltransferase

摘要

@@ The fungal indole prenyltransfereases (IPTs) are key enzymes that catalyze a prenylation of trypthophan or its derivatives with dimethylallyl diphosphate (DMAPP) as the prenyl donor in the biosynthesis of structurally diverse prenylated indole alkaloids such as ergot alkaloids and terrequinone alkaloids. The enzymes exhibit remarkable substrate tolerance for their aromatic substrates, and are thus are promising candidates as biocatalysts for further development of unnatural novel prenylated compounds. In particular, it is interesting since the prenylated natural products often exhibit higher or distinct biological and pharmaceutical activities from those of their precursors. Here we present precursor-directed biosynthesis of unnatural, novel prenylated indole polyphenols and carbazoles by exploring CdpNPT from Aspergillus fumigatus, which normally catalyzes a C5 prenylation of tryptophan-containing cyclic dipeptides at nitrogen of the indole core.