Discovery and heterologous expression of functional 4-Odimethylallyl-L-tyrosine synthases from lichen-forming fungi

Riccardo Iacovelli, Stella He, Nika Sokolova, Iris Lokhorst, Maikel Borg, Peter Fodran, Kristina Haslinger*

*Corresponding author for this work

Research output: Working paperPreprintAcademic

7 Downloads (Pure)

Abstract

ABSTRACT: Fungal DMATS-type aromatic prenyltransferases are a family of biosynthetic enzymes that catalyze the
prenylation of a range of aromatic substrates during the biosynthesis of bioactive indole alkaloids, diketopiperazines,
and meroterpenoids. Together with their broad substrate scope and soluble nature, this makes DMATS-type
prenyltransferases particularly adept for applications in biocatalysis, for example to derivatize aromatic drug leads and
improve their bioactivity. Here, we investigated four putative DMATS-type prenyltransferases from lichen-forming fungi,
an underexplored group of organisms that produce more than 1,000 unique metabolites. We were able to successfully
express two functional lichen prenyltransferases in the heterologous host A. oryzae, which allowed us to identify them as
4-O-dimethylallyltyrosine synthases. Our extensive bioinformatic analysis shows that related lichen prenyltransferases
are likely not active on indoles but rather on aromatic polyketides and phenylpropanoids, common metabolites in these
organisms. Overall, our work not only provides new insights into fungal DMATS-type prenyltransferases at the family
level, but it also enables future efforts aimed at identifying new candidates for biocatalytic transformations of aromatic
compounds.
Original languageEnglish
PublisherBioRxiv
Number of pages11
DOIs
Publication statusSubmitted - 23-Mar-2024

Cite this