The Gα protein AoGpaA regulates kojic acid production through the cAMP-PKA pathway in Aspergillus oryzae

Kojic acid is a secondary metabolite produced by some fungal species such as Aspergillus oryzae and has been used as a cosmetic ingredient for its skin-whitening effect. Despite its relatively simple structure, the biosynthetic pathway of kojic acid and how it is regulated have not yet been fully elucidated. In this study we examined whether Gα proteins are involved in the regulation of kojic acid production. We found that AoGpaA, one of the three Gα proteins in A. oryzae , plays an important role in this process, as kojic acid production was significantly delayed in the Δ AogpaA strain. Consistently, the expression of kojic acid biosynthetic genes was significantly reduced in the Δ AogpaA strain. Albeit its sequence similarity to mammalian Gi, it was highly likely that AoGpaA positively regulates cAMP synthesis, since the addition of cAMP to the culture medium or the overexpression of the catalytic subunit of protein kinase A restored kojic acid production. These results indicate that AoGpaA regulates kojic acid synthesis by positively regulating cAMP synthesis and the expression of kojic acid biosynthetic genes.