Profiling of secondary metabolite gene clusters regulated by LaeA in Aspergillus niger FGSC A1279 based on genome sequencing and transcriptome analysis

Abstract

The global regulator LaeA controls the production of many fungal secondary metabolites, possibly via chromatin remodeling. Here we aimed to survey the secondary metabolite profile regulated by LaeA in Aspergillus niger FGSC A1279 by genome sequencing and comparative transcriptomics between the laeA deletion (ΔlaeA) and overexpressing (OE-laeA) mutants. Genome sequencing revealed four putative polyketide synthase genes specific to FGSC A1279, suggesting that the corresponding polyketide compounds might be unique to FGSC A1279. RNA-seq data revealed 281 putative secondary metabolite genes upregulated in the OE-laeA mutants, including 22 secondary metabolite backbone genes. LC-MS chemical profiling illustrated that many secondary metabolites were produced in OE-laeA mutants compared to wild type and ΔlaeA mutants, providing potential resources for drug discovery. KEGG analysis annotated 16 secondary metabolite clusters putatively linked to metabolic pathways. Furthermore, 34 of 61 Zn2Cys6 transcription factors located in secondary metabolite clusters were differentially expressed between ΔlaeA and OE-laeA mutants. Three secondary metabolite clusters (cluster 18, 30 and 33) containing Zn2Cys6 transcription factors that were upregulated in OE-laeA mutants were putatively linked to KEGG pathways, suggesting that Zn2Cys6 transcription factors might play an important role in synthesizing secondary metabolites regulated by LaeA. Taken together, LaeA dramatically influences the secondary metabolite profile in FGSC A1279.