Effective production of kojic acid in engineered Aspergillus niger

Background Kojic acid (KA) is a widely used compound in the cosmetic, medical, and food industries, and is typically produced by Aspergillus oryzae . To meet increasing market demand, it is important to optimize KA production through seeking alternatives that are more economic than current A. oryzae -based methods. Results In this study, we achieved the first successful heterologous production of KA in Aspergillus niger , an industrially important fungus that does not naturally produce KA, through the expression of the kojA gene from A. oryzae . Using the resulting KA-producing A. niger strain as a platform, we identified four genes ( nrkA , nrkB , nrkC , and nrkD ) that negatively regulate KA production. Knocking down nrkA or deleting any of the other three genes resulted in a significant increase in KA production in shaking flask cultivation. The highest KA titer (25.71 g/L) was achieved in a pH controlled batch bioreactor using the kojA overexpression strain with a deletion of nrkC , which showed a 26.7% improvement compared to the KA titer (20.29 g/L) that was achieved in shaking flask cultivation. Conclusion Our study demonstrates the potential of using A. niger as a platform for studying KA biosynthesis and regulation, and for the cost-effective production of KA in industrial strain development.