Construction of yeast producing patchoulol by global metabolic engineering strategy
Construction of yeast producing patchoulol by global metabolic engineering strategy
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DOI：
10.1002/bit.27284
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发表时间：
2020-02-03
影响因子：
3.8
通讯作者：
Ogino, Hiroyasu
中科院分区：
文献类型：
--
作者：
Mitsui, Ryosuke;Nishikawa, Riru;Ogino, Hiroyasu
广藿香醇是在广藿香植物的叶子中发现的倍半萜醇，其可以通过蒸汽蒸馏提取。值得注意的是，广藿香醇是化学工业中经常使用的重要天然产品。然而，广藿香产生的广藿香醇量微不足道，更不用说蒸汽蒸馏，需要大量的能量和时间。可以在温和条件下培养并可以从可再生生物质资源中生产广藿香醇的重组微生物可能是一种有前途的替代品。我们以前开发的全球代谢工程策略（GMES），它产生了一个全面的代谢修饰酵母，使用鸡尾酒三角洲整合方法。本研究旨在通过对工程酵母的改造来生产广藿香醇。9个基因的表达参与广藿香醇合成的调制使用GMES。关于百香果醇的生产，所得菌株YPH 499/PAT 167/MVA 442分别显示出42.1mg/L的浓度、8.42mg/L/d的生产速率和2.05mg/g-葡萄糖的产量。与先前报道的重组微生物研究相比，本研究中通过分批发酵获得的这些浓度值、生产速率和产率均处于高水平。GMES可作为一种利用重组酿酒酵母生产植物次生代谢产物的潜在策略。
Patchoulol is a sesquiterpene alcohol found in the leaves of the patchouli plant that can be extracted by steam distillation. Notably, patchoulol is an essential natural product frequently used in the chemical industry. However, patchouli produces an insignificant amount of patchoulol, not to mention steam distillation, and requires a lot of energy and time. Recombinant microorganisms that can be cultured in mild conditions and can produce patchoulol from renewable biomass resources may be a promising alternative. We previously developed the global metabolic engineering strategy (GMES), which produces a comprehensive metabolic modification in yeast, using the cocktail delta-integration method. In this study, we aimed to produce patchoulol by modifying engineered yeast. The expression of nine genes involved in patchoulol synthesis was modulated using GMES. Regarding patchoulol production, the resultant strain, YPH499/PAT167/MVA442, showed a concentration of 42.1 mg/L, a production rate of 8.42 mg/L/d, and a yield of 2.05 mg/g-glucose, respectably. These concentration values, production rate, and yield obtained through batch-fermentation in this study were high level when compared to previously reported recombinant microorganism studies. GMES could be used as a potential strategy for producing secondary metabolites from plants in recombinant Saccharomyces cerevisiae.