Kojic acid (KA) is a representative secondary metabolite of Aspergillus oryzae, but the underlying molecular mechanisms that regulate KA production are unknown. This study tried to find a genetic factor of KA production in A. oryzae, with a special focus on liquid cultures. We screened a gene predicted to encode HirA, a subunit of the histone chaperon, the HIR complex. A gene disruption strain of hirA showed decreased KA production in liquid culture, whereas it showed increased KA production in plate culture. We confirmed that a decrease/increase of KA production observed by hirA disruption was caused by altered expression of kojA and kojR. These observations suggested the regulatory role of histone chaperon in secondary metabolism in filamentous fungi. So far as we know, this report is the first showing that disruption of a gene resulted in the opposite effect on KA production in liquid and plate cultures in...

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