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In recent years, many secondary metabolite gene clusters, including polyketide biosynthetic genes, non-ribosomal peptide synthetase genes have been uncovered through fungal genome sequencing. However, several transcriptome analyses revealed that a lot of biosynthetic genes are not activated in conventional culture condition. If we can systematically activate such silent biosynthetic gene clusters with genetic modification, it has a possibility of discovering novel natural products with previously unidentified unique structure and biological activities. In this study, we focused putative transcription factor (TF) genes which locating in the biosynthetic gene cluster. We conducted strong activity promoter-based overexpression of TFs in Aspergillus niger, Chaetomium globosum, Arthroderma otae, Trichophyton equinum, and could successfully biosynthesize secondary metabolites 1-9. These chemical structures were characterized based on MS and NMR spectroscopic analysis. The comprehensive relationship between gene clusters and natural products has allowed us to provide insight into their biosynthetic pathway.
