Journal Article Sirtuin A regulates secondary metabolite production by Aspergillus nidulans

Itoh, Eriko  ,  Shigemoto, Ryosuke  ,  Oinuma, Ken-Ichi  ,  Shimizu, Motoyuki  ,  Masuo, Shunsuke  ,  Takaya, Naoki

63 ( 4 )  , pp.228 - 235 , 2017-09 , Applied Microbiology, Molecular and Cellular Biosciences Research Foundation , 応用微生物学・分子細胞生物学研究奨励会
Late-stage cultures of filamentous fungi under nutrient starvation produce valuable secondary metabolites such as pharmaceuticals and pigments, as well as deleterious mycotoxins, all of which have remarkable structural diversity and wide-spectrum bioactivity. The fungal mechanisms regulating the synthesis of many of these compounds are not fully understood, but sirtuin A (SirA) is a key factor that initiates production of the secondary metabolites, sterigmatocystin and penicillin G, by Aspergillus nidulans. Sirtuin is a ubiquitous NAD+-dependent histone deacetylase that converts euchromatin to heterochromatin and silences gene expression. In this study, we have investigated the transcriptome of a sirA gene disruptant (SirAΔ), and found that SirA concomitantly repressed the expression of gene clusters for synthesizing secondary metabolites and activated that of others. Extracts of SirAΔ cultures grown on solid agar and analyzed by HPLC indicated that SirA represses the production of austinol, dehydroaustinol and sterigmatocystin. These results indicated that SirA is a transcriptional regulator of fungal secondary metabolism.

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