Metabolic engineering of Yarrowia lipolytica for liquiritigenin production

Liquiritigenin has broad applications in food and pharmaceutical industries. In this study, liquiritigenin was de novo biosynthesized in Yarrowia lipolytica for the first time. Twenty five genes from multiple species were screened and characterized for the efficient synthesis of liquiritigenin in Yarrowia lipolytica. Then, several metabolic engineering strategies were developed to increase liquiritigenin titer. Specifically, liquiritigenin titer was increased by 75% by fusing chalcone synthase and chalcone reductase, which effectively passed the intermediate produced from chalcone synthase to chalcone reductase. Engineering the length of promoters precisely manipulated the ratio of liquiritigenin and naringenin, thus generating two strains YL-603 and YL-604. In flask fermentation, the strain YL-604 produced 171 mg/L naringenin; while the strain YL-603 produced 62.4 mg/L liquiritigenin, which was 3.5-fold and 4.6-fold higher than the previously reported value in Escherichia coli and Saccharomyces cerevisiae, respectively. This study demonstrated that Y. lipolytica is an ideal host for liquiritigenin production.