The presented work focuses on the biosynthesis of fungal natural products. Structural analysis of phyllostictine A revealed the literature structure to be erroneous and led to the revised bicyclic 3-methylene tetramic acid. In particular, feeding 13 C-labeled precursors showed a haphazard incorporation into and set the basis for the correct structure elucidation. The Biosynthetic Gene Cluster (BGC) was identified by total genome sequencing of the producer (P. cirsii ) and in silico analyis. Targeted knock out experiments confirmed the BGC to be involved in phyllostictine A biosynthesis and produced an intermediate. In the attempt to define each biosynthetic step that takes part in Sch-642305 biosynthesis, two intermediates were observed after targeted knock out of a cytochrome P450 cytochrome and a flavoprotein oxidase, respectively. Genome assembly and in silico analysis showed over 150 BGC for this strain. The sch-related BGC was defined by rational survey and homology comparison with other producing organisms, such as Penicillium verrucosum and Penicillium brefeldianum, producers of Sch-642305 and Brefeldin A respectively. Although, other genes of Sch-642305 cluster were successfully disrupted, no other intermediate was observed.