These data have been curated at AspGD and were used as a criterion for our manual cluster boundary predictions (see below). An example of the inpA- and inpB-containing gene cluster determined by this criterion is shown in Figure 2. The gene clusters LEE011 solubility dmso of A. AZD1080 ic50 nidulans with all of the boundary predictions made with ‘expression pattern’ as the primary evidence are listed in Table 4. The total number of boundaries predicted using this criterion is summarized in Table 9. Figure 2 A. nidulans AN3497 gene cluster predicted based of gene expression analysis of Andersen et al.

2013. Red bar indicates manually predicted cluster boundary (AN3490-AN3497) based on expression pattern and aligned with orthologous clusters of A. versicolor and A. sydowii. Blue bar indicates SMURF boundary

prediction (AN3491-AN3506) and green bar indicates the antiSMASH-predicted boundary (AN3485-AN3503). Table 9 Summary of primary criteria used for making manual Emricasan concentration secondary metabolite gene cluster boundary predictions   ED EP ECS FA IGD A. nidulans 24 (18%) 38 (29%) 47 (36%) 17 (13%) 6 (4%) A. fumigatus 10 (15%) n/a 39 (57%) 7 (10%) 12 (18%) A. niger 0 (0%) n/a 129 (98%) 2 (<2%) 1 (<1%) A. oryzae 8 (6%) n/a 90 (73%) 17 (14%) 9 (7%) Abbreviations: ED, Experimentally determined; EP, Published expression pattern (M. Anderson et al, 2013); ECS, End of cluster synteny; FA, Change in functional annotation; IGD, Increase in intergenic distance; n/a, not applicable. To generate a high-quality set of candidate secondary metabolite biosynthetic gene clusters, we used SMURF and antiSMASH as the source of cluster predictions, along with manually predicted DTS clusters and then manually refined

3-oxoacyl-(acyl-carrier-protein) reductase the gene cluster boundaries. Manual cluster boundary annotations (Tables 4, 5, 6, 7 and Additional files 2, 3, 4, 5) were made based on several criteria: published experimental data (including gene expression studies), synteny between clustered genes among different species indicated by the presence of conserved gene cluster boundaries (Figure 1), functional annotation of predicted genes within and adjacent to clusters and increases in intergenic distance between boundary genes and adjacent genes, which we frequently observed (Figure 3). We determined that gene clusters tend to be conserved between species and that breaks in cluster synteny frequently indicate a cluster boundary. To the best of our knowledge, no gene cluster prediction algorithm or research group has used genomic comparisons between species for large-scale cluster predictions. We used the Sybil viewer [51], which displays alignments of orthologous genes across multiple species in their genomic context, to manually examine potential boundaries and to compare synteny between clusters of different species and/or strains (Figure 1) and the adjacent syntenic regions outside each predicted cluster. The genome sequence is available for two strains each of A. fumigatus (Af293 and A1163) and A.