Abstract 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.

中文翻译：

---

用于生产甘草素的解脂耶氏酵母的代谢工程

摘要 甘草素在食品和制药行业有着广泛的应用。在这项研究中，甘草素首次在解脂耶氏酵母中从头生物合成。对来自多个物种的 25 个基因进行了筛选和表征，以在解脂耶氏酵母中有效合成甘草素。然后，开发了几种代谢工程策略来增加甘草素的滴度。具体而言，通过融合查尔酮合酶和查尔酮还原酶，使甘草素的滴度提高了75%，有效地将查尔酮合酶产生的中间体传递给了查尔酮还原酶。设计启动子的长度可以精确控制甘草素和柚皮素的比例，从而产生两个菌株 YL-603 和 YL-604。在烧瓶发酵中，菌株YL-604产生171mg/L柚皮素；而菌株 YL-603 产生 62.4 mg/L 甘草素，分别比先前在大肠杆菌和酿酒酵母中报道的值高 3.5 倍和 4.6 倍。该研究表明，解脂耶氏酵母是生产甘草素的理想宿主。