MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin University of Science & Technology, Tianjin, 300457, China.
Microb Cell Fact. 2023 Feb 27;22(1):40. doi: 10.1186/s12934-023-02038-w.
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.
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.
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.
曲酸（KA）是一种广泛应用于化妆品、医学和食品行业的化合物，通常由米曲霉（Aspergillus oryzae）生产。为了满足不断增长的市场需求，通过寻找比当前基于米曲霉的方法更经济的替代方法来优化 KA 的生产非常重要。
在这项研究中，我们通过表达来自米曲霉的 kojA 基因，首次在不天然产生 KA 的工业上重要的黑曲霉（Aspergillus niger）中成功异源生产了 KA。利用产生 KA 的黑曲霉菌株作为平台，我们鉴定出四个负调控 KA 生产的基因（nrkA、nrkB、nrkC 和 nrkD）。敲低 nrkA 或删除其他三个基因中的任何一个，都会导致摇瓶培养中 KA 产量显著增加。在使用过表达 kojA 基因并缺失 nrkC 基因的菌株在 pH 控制的分批生物反应器中，KA 的最高产量（25.71 g/L）达到了 25.71 g/L，与摇瓶培养中达到的 KA 产量（20.29 g/L）相比提高了 26.7%。
我们的研究表明，黑曲霉可作为研究 KA 生物合成和调控的平台，以及在工业菌株开发中进行经济高效的 KA 生产的潜力。
