The impact of glutamine synthetase PbgsA on the growth, conidiation and mycophenolic acid production of Penicillium brevicompactum

Glutamine synthetase (GS) is a critical enzyme in nitrogen metabolism regulation and plays an essential role in the metabolic pathways involved in microbial growth and development. Penicillium brevicompactum, known for its rich repertoire of secondary metabolites, including mycophenolic acid (MPA), lacks research on the regulatory mechanisms of GS within this species. This study aimed to investigate the influence of GS on the growth, sporulation, and secondary metabolism of P. brevicompactum to elucidate the biological function of GS in this organism. We identified the glutamine synthetase gene (PbgsA) from P. brevicompactum and constructed PbgsA gene-overexpression and gene-silencing transformants. The impact of PbgsA on growth and sporulation was evaluated, revealing that PbgsA gene-overexpression transformants exhibited enhanced growth and significantly increased the expression levels of sporulation pathway genes (brlA, abaA, and wetA). Additionally, PbgsA gene-overexpression transformants produced higher MPA yields, with a maximum of 4.78 g/L, representing a 54.19 % increase compared to the wild type (WT). Conversely, PbgsA gene-silencing transformants showed reduced MPA production, with a minimum yield of 1.13 g/L, a 63.55 % decrease relative to the WT. Transcriptional analysis of the MPA biosynthetic gene cluster indicated that PbgsA exerted regulatory effects on certain biosynthetic pathway genes, such as mpaA and mpaB. This study demostrated the potential positive regulatory role of glutamine synthetase PbgsA in the growth, spore development, and secondary metabolism of P. brevicompactum, which provided a new strategy for genetic regulation in filamentous fungal.