Identification of local and cross-chromosomal biosynthetic gene clusters in filamentous fungi using gene expression data

Mikael R. Andersen, Jakob B.Nielsen, Andreas Klitgaard, Lene M. Petersen, Tilde J. Hansen, Lene H. Blicher, Charlotte H. Gottfredsen, Thomas O. Larsen, Kristian F. Nielsen, Uffe H. Mortensen

Author address: 

Department of Systems Biology, Technical University of Denmark, Kgs Lyngby, Denmark

Abstract: 

Biosynthetic pathways of secondary metabolites from fungi are currently subject to an intense effort to elucidate the genetic basis for these compounds due to their large potential within pharmaceutics and synthetic biochemistry. The preferred method is methodological gene deletions to identify supporting enzymes for key synthases one cluster at a time. In earlier work we presented a method for using a gene expression compendium to accurately predict co-regulated gene clusters in general, and in particular the members of gene clusters for secondary metabolism. A benchmarking of the method in Aspergillus nidulans by comparison to previous gene deletion studies showed the method to be accurate in 13 out of 16 known clusters and nearly accurate for the remaining three. In this work, we have expanded the algorithm to identify cross-chemistry between physically separate gene clusters (super clusters), and validate this both with legacy data and experimentally by prediction and verification of a new supercluster consisting of the non-ribosomal peptide synthetase (NRPS) AN1242 (on chr VIII) and the prenyltransferase AN11080 (on chromosome V) as well as identication of the shared product compound nidulanin A. We also propose further implications of the gene clustering, as our analysis shows that approximately 10 % of the genes seem to be non-randomly (p
2013

abstract No: 

N/A

Full conference title: 

27th Fungal Genetics Conference
    • Fungal Genetics Conference 27th (2013)