title: Identification and characterization of Penicillium                      citrinum VeA and LaeA as global regulators for ML-236B production.
abstract: In filamentous fungi, production of multiple secondary metabolites is controlled by so-called global regulators. In this study, two genes encoding homologs of VeA and LaeA, representative fungal global regulators, were identified in ML-236B-producing Penicillium citrinum. Disruption of VeA and/or LaeA and complementation clearly demonstrated that both of them played critical roles in ML-236B production by controlling the expression of mlcR, the pathway-specific activator gene for ML-236B biosynthesis. Moreover, sequence analysis revealed that laeA in a mutant strain producing high levels of ML-236B (strain S-1567) possessed a single nucleotide alteration, which resulted in 15 surplus amino acids at the carboxyl terminus of LaeA compared to the LaeA in the wild-type strain (strain SANK18767). Introduction of the mutated laeA into SANK18767 proved that the extended carboxyl region plays a crucial role in the higher production of ML-236B. These results indicated that VeA and LaeA dominantly control the biosynthesis of ML-236B, and the enhanced production in the strain S-1567 is attributable to the mutation in laeA.
authors.affiliation: International Center for Biotechnology, Osaka University, Yamadaoka, Suita, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Baba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Takuya
authors.initials: T
authors.lastname: Nihira
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D015966:Gene Expression Regulation, Fungal; D005809:Genes, Regulator; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009154:Mutation; D010407:Penicillium / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C012258:mevastatin; D008148:Lovastatin