Overexpression of the laeA gene leads to increased production of cyclopiazonic acid in Aspergillus fumisynnematus

• Published in: Fungal biology Vol. 119; no. 11; pp. 973 - 983
• Main Authors: Hong, Eun Jin, Kim, Na Kyeong, Lee, Doyup, Kim, Won Gon, Lee, Inhyung
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2015
• Subjects: Aspergillus - cytology; Aspergillus - genetics; Aspergillus - growth & development; Aspergillus - metabolism; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Gene Expression; Genes, Fungal; Genes, Regulator; Indoles - metabolism; Mass Spectrometry; Pigments, Biological - metabolism; Promoter Regions, Genetic; Secondary Metabolism; Secondary metabolite; Spores, Fungal - growth & development; Secondary metabolite
• ISSN: 1878-6146; 1878-6162
• DOI: 10.1016/j.funbio.2015.06.006

To explore novel bioactive compounds produced via activation of secondary metabolite (SM) gene clusters, we overexpressed an ortholog of laeA, a gene that encodes a global positive regulator of secondary metabolism in Aspergillus fumisynnematus F746. Overexpression of the laeA gene under the alcA promoter resulted in the production of less pigment, shorter conidial head chains, and fewer conidia. Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis revealed that SM production in OE::laeA was significantly increased, and included new metabolites that were not detected in the wild type. Among them, a compound named F1 was selected on the basis of its high production levels and antibacterial effects. F1 was purified by column chromatography and preparative TLC and identified as cyclopiazonic acid (CPA) by LC/MS, which had been previously known as mycotoxin. As A. fumisynnematus was not known to produce CPA, these results suggest that overexpression of the laeA gene can be used to explore the synthesis of useful bioactive compounds, even in a fungus for which the genome sequence is unavailable. •The laeA gene was cloned and sequenced in Aspergillus fumisynnematus for the first time.•An OE::laeA showed shorter conidial head chains and fewer conidia than WT.•The SM production was increased in OE::laeA with putative new metabolites.•The production of CPA was observed in A. fumisynnematus for the first time.•We suggest cautious applications of OE::laeA for manufacturing functional foods.