SMURF: Genomic mapping of fungal secondary metabolite clusters

Abstract

Fungi produce an impressive array of secondary metabolites (SMs) including mycotoxins, antibiotics and pharmaceuticals. The genes responsible for their biosynthesis, export, and transcriptional regulation are often found in contiguous gene clusters. To facilitate annotation of these clusters in sequenced fungal genomes, we developed the web-based software SMURF (www.jcvi.org/smurf/) to systematically predict clustered SM genes based on their genomic context and domain content. We applied SMURF to catalog putative clusters in 27 publicly available fungal genomes. Comparison with genetically characterized clusters from six fungal species showed that SMURF accurately recovered all clusters and detected additional potential clusters. Subsequent comparative analysis revealed the striking biosynthetic capacity and variability of the fungal SM pathways and the correlation between unicellularity and the absence of SMs. Further genetics studies are needed to experimentally confirm these clusters.

Figure 1

Numbers of backbone genes and SM clusters in the 27 sequenced fungal genomes we analyzed. The central columns show the numbers of backbone genes of each type in a species. Each column contains two numbers separated by a slash; the first (in bold) is the number of backbone genes, and the second is the number of putative SM clusters predicted by SMURF. If both numbers are identical, only one (in bold) is shown. The tree topology is based on the phylogenetic tree by Fitzpatrick and colleagues (Figure 2 in (Fitzpatrick et al., 2006)). Species named in red are human pathogens (some are also animals and/or plant pathogens), blue are plant pathogens, and black are non-pathogenic fungi. Red bullets mark two internal branches on which enrichment in backbone genes occurred during evolution. In the histograms on the right, green bars show the total numbers of SM clusters predicted by SMURF in each genome (excluding SM clusters containing only PKS-like and NRPS-like genes), and purple bars show the numbers of SM clusters that have been characterized experimentally. PKS, polyketide synthase; DMATS, prenyltransferase; NRPS, nonribosomal peptide synthase.

Figure 2. Core orthologous and species-specific SM clusters in A. fumigatus, A. clavatus and N. fischeri

This Venn diagram shows relationships between putative SM clusters that were identified by SMURF in these three species. Non-overlapping areas represent the number of clusters unique to each species. Overlapping areas represent the number of orthologous clusters shared by two or three species. The total number of clusters is shown under the species name. The figure is not drawn to scale.