biostudies-literatureUnknown13Kealey JTLichen-forming fungi produce a variety of secondary metabolites including bioactive polyketides. Advances in DNA and RNA sequencing have led to a growing database of new lichen gene clusters encoding polyketide synthases (PKS) and associated ancillary activities. Definitive assignment of a PKS gene to a metabolic product has been challenging in the lichen field due to a lack of established gene knockout or heterologous gene expression systems. Here, we report the reconstitution of a non-reducing PKS gene from the lichen <i>Pseudevernia furfuracea</i> and successful heterologous expression of the synthetic lichen PKS gene in engineered <i>Saccharomyces cerevisiae</i>. We show that <i>P. furfuracea</i> PFUR17_02294 produces lecanoric acid, the depside dimer of orsellinic acid, at 360 mg/L in small-scale yeast cultures. Our results unequivocally identify PFUR17_02294 as a lecanoric acid synthase and establish that a single lichen PKS synthesizes two phenolic rings and joins them by an ester linkage to form the depside product.Metabolic engineering communicationse00172https://www.ebi.ac.uk/biostudies/studies/S-EPMC8365352biostudies-literatureIdentification of a lichen depside polyketide synthase gene by heterologous expression in <i>Saccharomyces cerevisiae</i>.PMC8365352Kealey JTCraig JPBarr PJfalseIdentification of a lichen depside polyketide synthase gene by heterologous expression in <i>Saccharomyces cerevisiae</i>.Lichen-forming fungi produce a variety of secondary metabolites including bioactive polyketides. Advances in DNA and RNA sequencing have led to a growing database of new lichen gene clusters encoding polyketide synthases (PKS) and associated ancillary activities. Definitive assignment of a PKS gene to a metabolic product has been challenging in the lichen field due to a lack of established gene knockout or heterologous gene expression systems. Here, we report the reconstitution of a non-reducing PKS gene from the lichen <i>Pseudevernia furfuracea</i> and successful heterologous expression of the synthetic lichen PKS gene in engineered <i>Saccharomyces cerevisiae</i>. We show that <i>P. furfuracea</i> PFUR17_02294 produces lecanoric acid, the depside dimer of orsellinic acid, at 360 mg/L in small-scale yeast cultures. Our results unequivocally identify PFUR17_02294 as a lecanoric acid synthase and establish that a single lichen PKS synthesizes two phenolic rings and joins them by an ester linkage to form the depside product.2021-01-01T00:00:00Z2021 Dec2024-11-15T03:23:24.227Z2022-02-11T09:47:33.451ZS-EPMC83653523443020210.1016/j.mec.2021.e00172