Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum

SummaryPenicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. Here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. Gene deletions confirmed that two nonreducing PKSs (NRPKSs), vrtA and gsfA, are required for the biosynthesis of 1 and 2, respectively. Both PKSs share similar domain architectures and lack a C-terminal thioesterase domain. We identified gsfI as the chlorinase involved in the biosynthesis of 2, because deletion of gsfI resulted in the accumulation of decholorogriseofulvin 3. Comparative analysis with the P. chrysogenum genome revealed that both clusters are embedded within conserved syntenic regions of P. aethiopicum chromosomes. Discovery of the vrt and gsf clusters provided the basis for genetic and biochemical studies of the pathways.

Graphical AbstractFigure optionsDownload high-quality image (522 K)Download as PowerPoint slideHighlights
► 454 sequencing unveiled the gene clusters for viridicatumtoxin 1 and griseofulvin 2
► vrt and gsf clusters lie within conserved syntenic regions of P. aethiopicum genome
► VrtA and GsfA are nonreducing PKSs required for biosynthesis of 1 and 2
► gsfI encodes chlorinase involved in the biosynthesis of 2