Holm, Dorte Koefoed1; Petersen, Lene Maj1; Klitgaard, Andreas7; Knudsen, Peter Boldsen1; Jarczynska, Zofia Dorota1; Nielsen, Kristian Fog1; Gotfredsen, Charlotte Held6; Larsen, Thomas Ostenfeld1; Mortensen, Uffe Hasbro1
1 Department of Systems Biology, Technical University of Denmark2 Metabolic Signaling and Regulation, Department of Systems Biology, Technical University of Denmark3 Fungal Physiology and Biotechnology, Department of Systems Biology, Technical University of Denmark4 Eucaryotic Molecular Cell Biology, Department of Systems Biology, Technical University of Denmark5 Metabolomics Platform, Department of Systems Biology, Technical University of Denmark6 Department of Chemistry, Technical University of Denmark7 Office for HR, Administration, Technical University of Denmark
Secondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA.
Chemistry and Biology, 2014, Vol 21, Issue 4, p. 519-529