Aromatic prenyltransferases catalyse the addition of an isoprenoid moiety to an aromatic core, typically a phenol or indole derived scaffold. These prenylated cores are further modified by cyclisations, oxidations and reductions to produce a diverse array of natural molecules with a range of bioactive properties. These prenyltransferases represent central targets for structure and function-based investigations since prenylation contributes significantly to structural diversity.
One class of structurally diverse natural molecules is the indole diterpenes. Indole diterpenes are indole alkaloid derivatives, part of the secondary metabolism of a group of related fungi, that have been shown to possess diverse bioactive properties. Nodulisporic acid A, an indole diterpene possessing remarkable insecticidal activity, is proposed to be synthesised using a pair of indole prenyltransferases, termed NodD1 and NodD2.
In the present work, the genomic, kinetic, and structural features of NodD1 and NodD2 are being compared against known fungal indole prenyltransferases to aid in our understanding of how these enzymes function. This will help to understand the construction of prenylated indole derivates in nature and will inform redesign of these enzymes to accommodate unnatural substrates.