title: Overexpression of the laeA gene leads to increased production of cyclopiazonic acid in Aspergillus fumisynnematus.
abstract: 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.
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Hong
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Na Kyeong
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Doyup
authors.initials: D
authors.lastname: Lee
authors.affiliation: Functional Metabolite Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-806, Republic of Korea.
authors.forename: Won Gon
authors.initials: WG
authors.lastname: Kim
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea. Electronic address: leei@kookmin.ac.kr.
authors.forename: Inhyung
authors.initials: I
authors.lastname: Lee
mesh_terms: D001230:Aspergillus / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D015870:Gene Expression; D005800:Genes, Fungal; D005809:Genes, Regulator; D007211:Indoles / Q000378:metabolism*; D013058:Mass Spectrometry; D010860:Pigments, Biological / Q000378:metabolism; D011401:Promoter Regions, Genetic; D064210:Secondary Metabolism; D013172:Spores, Fungal / Q000254:growth & development
chemical_list: D007211:Indoles; D010860:Pigments, Biological; C000543:cyclopiazonic acid
keywords: Secondary metabolite