Chemistry Special Seminar - Dr. John Sorensen

Title:

The untapped potential of natural product biosynthesis in lichen fungi: opportunities and challenges

Abstract: 

Lichen fungi remain one of the most underdeveloped sources of novel bioactive natural products. This is in 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 biosynthetic potential of the lichen Cladonia uncialis. We have carried out the sequencing, assembly and annotation of the genome and as a result, we have identified approximately 50 biosynthetic gene clusters that code for small molecule biosynthesis.  A large number of these clusters have a gene that codes for a polyketide synthase.  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. This genome sequencing has revealed the rich biosynthetic potential of lichen fungi.

More recently, we have been using the filamentous fungus Aspergillus oryaze as platform for heterologous expression of biosynthetic genes. We have focused on the gene cluster involved in usnic acid biosynthesis, as well as other polyketide synthases. This talk will outline the challenges that we have encountered in heterologous expression of biosynthetic genes from C. uncialis in A. oryaze.  This talk will present some of the success and challenges that we have had with the A. oryaze platform. A strategy for overcoming some of the challenges observed with heterologous expression will also be described.