Satoshi BabaHiroshi KinoshitaTakuya NihiraOsaka UniversityDaiichi Sankyo Kabushiki-gaishaMahidol University2018-06-112018-06-112012-02-01Current Genetics. Vol.58, No.1 (2012), 1-1114320983017280832-s2.0-84857041431https://repository.li.mahidol.ac.th/handle/20.500.14594/13810In 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. © 2011 Springer-Verlag.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1007/s00294-011-0359-x