초록
<P>Arbutin, a glycoside, is derived from the leaves of several plants, including wheat, pear, and bearberry plants, and has a significant role in the treatment of melanoma, cystitis, and cough. Here, we aimed to modify <I>Yarrowia lipolytica</I> to produce arbutin. To construct the arbutin synthetic pathway in <I>Y. lipolytica</I>, three genes (chorismate pyruvate-lyase (UbiC), 4-hydroxybenzoate 1-hydroxylase (MNX1), and hydroquinone glucosyltransferase (AS)) were codon-optimized and heterologously expressed. To maximize arbutin production, seven arbutin-biosynthesis molecular targets were overexpressed, and we found that the individual strengthening of <I>DHS1</I> and <I>DHS2</I> led to an 8.9- and 7.8-fold improvement in arbutin yield, respectively. Through optimization, a maximum arbutin titer of 8.6 ± 0.7 g/L was achieved using the finally engineered strain, po1f-At09. Overall, this is the first report of heterologous arbutin synthesis in <I>Y. lipolytica</I> at a high titer. Furthermore, this work opens a possibility for the overproduction of shikimate pathway derivatives in <I>Y. lipolytica</I>.</P><BR>[FIG OMISSION]</BR>