Discovery and linking of genes to biosynthetic pathways in Aspergillus

Aspergilli constitute an important group of fungi, including species used by the pharma and biotech industries, as well as mycotoxin producing contaminants. We are involved in a huge genome sequencing project, including all described Aspergillus species, paving the way for genomics driven research into fungal secondary metabolism. Aspergilli are capable of producing hundreds of secondary metabolites (SMs), why rapid and automated identification of known compounds (dereplication) using UHPLC-DAD-HRMS/MS based methods is crucial for discovery and pathway elucidation.¹ Our efforts towards linking of genes to their corresponding biosynthetic pathways have been focused on non-reduced polyketides such as orsellinic acids and 6-methyl-salicylic acid, including characterization of the yanuthone D biosynthetic pathway in A. niger.² This paper will highlight our most recent genomics driven efforts towards accurate prediction and discovery of novel pathways and bioactive compounds.³

1.  Klitgaard, A., Nielsen, A., Andersen, M.R., Larsen, T.O., Frisvad, J.C., Nielsen, K.F. (2013). Aggressive dereplication using UHPLC-DAD-QTOF – screening extracts for up to 3000 fungal secondary metabolites in 30 seconds. Analytical and Bioanalytical Chemistry, 406, 1933-1943.
2. Holm, D.K., Petersen, L.M., Klitgaard, A., Knudsen, P.B., Jarczynska, S.D., Nielsen, K.F., Gotfredsen, C.H., Larsen, T.O., Mortensen, U.H. (2014). Molecular and chemical characterization of the biosynthesis of the 6-MSA derived meroterpenoid yanuthone D in Aspergillus niger. Chemistry & Biology, 21, 519-529.
3. Andersen, M.R., Nielsen, J.B., Klitgaard, A., Petersen, L.M., Zachariasen, M., Hansen, T.J., Blicher, L.H., Gotfredsen, C.H., Larsen, T.O., Nielsen, K.F. & Mortensen, U.H. (2013). Accurate prediction of secondary metabolite gene clusters in filamentous fungi. PNAS, 110, 99-107.