Engineering Yarrowia lipolytica for Enhanced Production of Arbutin. 2020

Yanzhe Shang, and Wenping Wei, and Ping Zhang, and Bang-Ce Ye
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering , East China University of Science and Technology , Shanghai 200237 , China.

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 Yarrowia lipolytica to produce arbutin. To construct the arbutin synthetic pathway in Y. lipolytica, 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 DHS1 and DHS2 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 Y. lipolytica at a high titer. Furthermore, this work opens a possibility for the overproduction of shikimate pathway derivatives in Y. lipolytica.

UI MeSH Term Description Entries
D001104 Arbutin
D012765 Shikimic Acid A tri-hydroxy cyclohexene carboxylic acid metabolite of the shikimate pathway. It is important in the biosynthesis of aromatic amino acids, flavonoids and alkaloids in plants and microorganisms. 1-Cyclohexene-1-carboxylic acid, 3,4,5-trihydroxy-, (3R-(3alpha,4alpha,5beta))-,Shikimates,Shikimic Acid Derivatives,Acid, Shikimic
D060847 Metabolic Engineering Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS. Engineering, Metabolic
D025062 Yarrowia A genus of ascomycetous yeast in the family Dipodascaceae, order SACCHAROMYCETALES. Yarrowia lipolytica,Yarrowias

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