Lichen fungi remain one of the most underdeveloped sources of novel bioactive natural products. In large part this is due to challenges that result from the slow growth of the symbiotic organism. Our research program has been focused on examining the biosynthesis of natural products in lichen fungi by identifying biosynthetic gene clusters in the genome of the model organism Cladonia uncialis. We have carried out the sequencing, assembly and annotation of the genome of C. uncialis. As a result, we have identified approximately 50 unique biosynthetic gene clusters that appear to code for small molecule biosynthesis. The majority of these gene clusters have a gene that codes for a polyketide synthase that is involved in the key assembly of the carbon skeleton. Numerous accessory genes, such as methyl transferases and hydroxylases, flank each of these polyketide synthase genes. Based on homology to genes characterized from non-lichen fungi we have been able to propose function for some of these gene clusters. Our recent focus has been on conclusively assigning function of these genes by heterologous expression in the filamentous fungi Aspergillus oryaze. In particular we have been focusing on the expression of the gene cluster involved in usnic acid biosynthesis. This talk will focus on our recent results from the heterologous expression of this and numerous other genes from C. uncialis in A. oryaze. We will present some of the challenges that we have discovered in achieving successful heterologous expression. We will describe our plans to overcome some of these challenges

Linking genes to molecules in lichen fungi: Challenges with heterologous expression

2019 Fall National Meeting

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