Biosynthesis of a Functional Human Milk Oligosaccharide, 2′-Fucosyllactose, and l-Fucose Using Engineered Saccharomyces cerevisiae,ACS Synthetic Biology

当前位置： X-MOL 学术 › ACS Synth. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Biosynthesis of a Functional Human Milk Oligosaccharide, 2′-Fucosyllactose, and l-Fucose Using Engineered Saccharomyces cerevisiae
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-10-16 00:00:00 , DOI: 10.1021/acssynbio.8b00134
Jing-Jing Liu ₁ , Suryang Kwak _{1,

2} , Panchalee Pathanibul ₂ , Jae Won Lee ₂ , Sora Yu ₃ , Eun Ju Yun _{1,

3} , Hayoon Lim ₁ , Kyoung Heon Kim ₃ , Yong-Su Jin _{1,

2}

Affiliation

2′-fucosyllactose (2-FL), one of the most abundant human milk oligosaccharides (HMOs), has received much attention due to its health-promoting activities, such as stimulating the growth of beneficial gut microorganisms, inhibiting pathogen infection, and enhancing the host immune system. Consequently, large quantities of 2-FL are on demand for food applications as well as in-depth investigation of its biological properties. Biosynthesis of 2-FL has been attempted primarily in Escherichia coli, which might not be the best option to produce food and cosmetic ingredients due to the presence of endotoxins on the cell surface. In this study, an alternative route to produce 2-FL via a de novo pathway using a food-grade microorganism, Saccharomyces cerevisiae, has been devised. Specifically, heterologous genes, which are necessary to achieve the production of 2-FL from a mixture of glucose and lactose, were introduced into S. cerevisiae. When the lactose transporter (Lac12), de novo GDP-l-fucose pathway (consisting of GDP-d-mannose-4,6-dehydratase (Gmd) and GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase (WcaG)), and α1,2-fucosyltransferase (FucT2) were introduced, the resulting engineered strain (D452L-gwf) produced 0.51 g/L of 2-FL from a batch fermentation. In addition, 0.41 g/L of l-fucose was produced when α-l-fucosidase was additionally expressed in the 2-FL producing strain (D452L-gwf). To our knowledge, this is the first report of 2-FL and l-fucose production in engineered S. cerevisiae via the de novo pathway. This study provides the possibility of producing HMOs by a food-grade microorganism S. cerevisiae and paves the way for more HMO production in the future.

中文翻译：

工程化酿酒酵母生物合成功能性人乳寡糖，2'-岩藻糖和L-岩藻糖

2'-岩藻糖半乳糖（2-FL）是最丰富的人乳寡糖（HMO）之一，由于其促进健康的活动（例如刺激有益肠道微生物的生长，抑制病原体感染和增强健康）而受到了广泛关注。宿主免疫系统。因此，对于食品应用以及对其生物学性质的深入研究，需要大量的2-FL。主要在大肠杆菌中尝试了2-FL的生物合成，由于细胞表面存在内毒素，它可能不是生产食品和化妆品成分的最佳选择。在这项研究中，另一种使用食品级微生物酿酒酵母通过从头途径生产2-FL的途径，已经设计好了。具体地，将异源基因引入酿酒酵母中，所述异源基因是从葡萄糖和乳糖的混合物中产生2-FL所必需的。当乳糖转运蛋白（Lac12）从头产生GDP- 1-岩藻糖途径（由GDP- d-甘露糖-4,6-脱水酶（Gmd）和GDP-4-酮-6-脱氧甘露糖-3,5-表异构酶-组成引入4-还原酶（WcaG）和α1,2-岩藻糖基转移酶（FucT2），所得的工程菌株（D452L-gwf）通过分批发酵产生了0.51 g / L的2-FL。另外，当α- l时产生0.41g / L的l-岩藻糖。-岩藻糖苷酶在产生2-FL的菌株（D452L-gwf）中另外表达。据我们所知，这是通过从头途径在工程酿酒酵母中产生2-FL和1-岩藻糖的首次报道。这项研究提供了由食品级微生物酿酒酵母生产HMO的可能性，并为将来更多的HMO生产铺平了道路。

更新日期：2018-10-16

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11