A candidate gene cluster for the bioactive natural product gyrophoric acid in lichen-forming fungi

  • Natural products of lichen-forming fungi are structurally diverse and have a variety of medicinal properties. Despite this, they a have limited implementation in industry, because the corresponding genes remain unknown for most of the natural products. Here we implement a long-read sequencing and bioinformatic approach to identify the biosynthetic gene cluster of the bioactive natural product gyrophoric acid (GA). Using 15 high-quality genomes representing nine GA-producing species of the lichen-forming fungal genus Umbilicaria, we identify the most likely GA cluster and investigate cluster gene organization and composition across the nine species. Our results show that GA clusters are promiscuous within Umbilicaria, with only three genes that are conserved across species, including the PKS gene. In addition, our results suggest that the same cluster codes for different but structurally similar NPs, i.e., GA, umbilicaric acid and hiascic acid, bringing new evidence that lichen metabolite diversity is also generated through regulatory mechanisms at the molecular level. Ours is the first study to identify the most likely GA cluster, and thus provides essential information to open new avenues for biotechnological approaches to producing and modifying GA and similar lichen-derived compounds. We show that bioinformatics approaches are useful in linking genes and potentially associated natural products. Genome analyses help unlocking the pharmaceutical potential of organisms such as lichens, which are biosynthetically diverse but slow growing, and difficult to cultivate due to their symbiotic nature.

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Author:Garima SinghORCiDGND, Anjuli CalcheraORCiDGND, Dominik MergesORCiDGND, Jürgen OtteGND, Imke SchmittORCiDGND, Francesco Dal GrandeORCiD
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2022/01/16
Date of first Publication:2022/01/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/04/20
Page Number:44
Institutes:Angeschlossene und kooperierende Institutionen / Senckenbergische Naturforschende Gesellschaft
Biowissenschaften / Institut für Ökologie, Evolution und Diversität
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY-ND - Namensnennung - Keine Bearbeitungen 4.0 International