Assessing medium constituents for optimal heterologous production of anhydromevalonolactone in recombinant Aspergillus oryzae

Anhydromevalonolactone (AMVL) is a bioactive natural product that arises from a molecular biology technique using Aspergillus oryzae as a heterologous host. AMVL has been used as a precursor for the synthesis of insect pest control reagents and has numerous applications in the biotechnological and medical industries. In this study, the Plackett-Burman Design and the Central Composite Design, which offer efficient and feasible approaches, were complemented to screen significant parameters and identify the optimal values for maximum AMVL production. The results suggested that sucrose, NaNO3, yeast extract and K2HPO4 were the key factors affecting AMVL production in a complex medium, whereas the major components required for a defined medium were NaNO3, K2HPO4, KH2PO4 and trace elements. These factors were subsequently optimized using the response surface methodology. Under optimal conditions, a maximum AMVL production of 250 mg/L in the complex medium and 200 mg/L in the defined medium was achieved, which represents an increase of approximately 3-4-fold compared to the commonly used malt extract medium.