For example, A. nidulans bglD (AN7915)
encodes a glucosidase present in the F9775 biosynthetic gene cluster (Additional file 2). In a cclAΔ strain background in which histone 3 lysine 4 methylation is impaired, the expression of cryptic secondary metabolite clusters, such as F9775, is activated . The activation of bglD expression was observed along with other genes in the F9775 cluster and based on this pattern of coregulation, bglD is included as a member of this cluster . It is unclear, however, whether bglD actually plays a role in F9775 biosynthesis. The gene encoding translation elongation factor 1 gamma, stcT, is a member of the ST gene cluster (stc) of A. nidulans. Its Gamma-secretase inhibitor inclusion in the stc cluster was based on its pattern of coregulation with 24 other genes, some of which have experimentally determined roles in A. nidulans
ST biosynthesis, or are orthologous to A. parasiticus proteins involved selective HDAC inhibitors in AF production, for which ST is a precursor . We also observed a gene, AN2546, that is expressed, and is predicted to encode a glycosylphosphatidylinositol (GPI)-anchored protein , located in the emericellamide cluster (Additional file 2); however, an AN2546 deletion strain still produces emericellamide, thus its inclusion in the cluster is based on its genomic location and expression pattern rather than function. These examples indicate that some genes are located within clusters and yet may not contribute to secondary metabolite production. The frequency and significance of unrelated genes that have become incorporated into a secondary metabolism gene cluster remains unclear; experimental verification is needed to further assess these. Ribonuclease T1 In cases where the cluster synteny data were compelling, cluster synteny was given higher precedence than functional annotation in the delineation of the cluster boundaries. Increases in the distance between predicted boundary genes
and the gene directly adjacent to a boundary (which we refer to as intergenic distance) were frequently observed. An example with a large intergenic distance at the right boundary is shown in the A. fumigatus gliotoxin (gli) cluster (Figure 3). However, we found that more subtle increases in intergenic distance were only somewhat reliable when compared to boundaries with experimental evidence. We therefore only based a cluster boundary prediction on an increase in intergenic distance in a small number of cases where no other data were available (Table 9). Discussion AspGD provides high-quality manual and computational gene structure and function annotations for A. nidulans, A. fumigatus, A. niger and A. oryzae, along with sequence analysis and visualization resources for these and additional Aspergilli and related species. Among fungal databases, AspGD is the only resource performing comprehensive manual literature curation for Aspergillus species. AspGD contains curated data covering the entire corpus of experimental literature for A. nidulans, A. fumigatus, A.