Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering , East China University of Science and Technology , Shanghai 200237 , China.
School of Chemistry and Chemical Engineering , Shihezi University , Xinjiang 832000 , China.
J Agric Food Chem. 2020 Feb 5;68(5):1364-1372. doi: 10.1021/acs.jafc.9b07151. Epub 2020 Jan 24.
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 to produce arbutin. To construct the arbutin synthetic pathway in , 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 and 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 at a high titer. Furthermore, this work opens a possibility for the overproduction of shikimate pathway derivatives in .
熊果苷是一种糖苷，来源于包括小麦、梨和熊果在内的几种植物的叶子，在治疗黑色素瘤、膀胱炎和咳嗽方面有显著作用。在这里，我们旨在通过 来生产熊果苷。为了在 中构建熊果苷的合成途径，我们对三个基因（分支酸丙酮酸-裂解酶（UbiC）、4-羟基苯甲酸 1-羟化酶（MNX1）和对羟基苯葡萄糖苷转移酶（AS））进行了密码子优化和异源表达。为了最大限度地提高熊果苷的产量，我们过表达了七个熊果苷生物合成的分子靶点，发现单独强化 和 分别使熊果苷的产量提高了 8.9 倍和 7.8 倍。通过优化，最终工程菌株 po1f-At09 的熊果苷最高产量达到了 8.6±0.7 g/L。总的来说，这是首次在 中以高产异源合成熊果苷的报道。此外，这项工作为在 中过量生产莽草酸途径衍生物开辟了可能性。
