Elucidating the biosynthetic pathway of Felinone A in Aspergillus nidulans through serial promoter replacement

Yien Liao Tzu Shyang Lin Clay Wang
School of Pharmacy, University of Southern California, Los Angeles, California, USA

Fungal secondary metabolites (SMs) are an important source for drug discovery. Thousands of biosynthetic pathways of SMs are revealed by several approaches and classified based on their characteristics. Felinone A, recently discovered in marine fungus, belongs to azaphilones – a set of SMs that contains many compounds with potent biological activities. In our previous study, we replaced the promoter of nonreducing polyketides synthase (NR-PKS) AN7901 and isolated 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)-benzaldehyde (compound 1)1. However, since we did not activate the surrounding genes that may modify compound 1, the final product of this gene cluster remains unknown. By homolog comparison, we propose that AN7901 is involved in the biosynthetic pathway of Felinone A, which isthe final product, and that compound 1 is an intermediate2. We conducted BLAST analysis to determine the putative biosynthesis genes involved, and will replace their promoters serially. The data will allow us to confirm our proposed biosynthetic pathway and determine the boundary of Felinone A cluster.