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工程化微生物途径合成人乳寡糖。

Engineered Microbial Routes for Human Milk Oligosaccharides Synthesis.

机构信息

Department of Food Science, College of Agriculture and Life Sciences, Cornell University, 411 Tower Road, Ithaca, New York 14853, United States.

出版信息

ACS Synth Biol. 2021 May 21;10(5):923-938. doi: 10.1021/acssynbio.1c00063. Epub 2021 Apr 28.

Abstract

Human milk oligosaccharides (HMOs) are one of the important ingredients in human milk, which have attracted great interest due to their beneficial effect on the health of newborns. The large-scale production of HMOs has been researched using engineered microbial routes due to the availability, safety, and low cost of host strains. In addition, the development of molecular biology technology and metabolic engineering has promoted the effectiveness of HMOs production. According to current reports, 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto--tetraose (LNT), lacto--neotetraose (LNnT), 3'-sialyllactose (3'-SL), 6'-sialyllactose (6'-SL), and some fucosylated HMOs with complex structures have been produced the engineered microbial route, with 2'-FL having been produced the most. However, due to the uncertainty of metabolic patterns, the selection of host strains has certain limitations. Aside from that, the expression of appropriate glycosyltransferase in microbes is key to the synthesis of different HMOs. Therefore, finding a safe and efficient glycosyltransferase has to be addressed when using engineered microbial pathways. In this review, the latest research on the production of HMOs using engineered microbial routes is reported. The selection of host strains and adapting different metabolic pathways helped researchers designing engineered microbial routes that are more conducive to HMOs production.

摘要

人乳寡糖(HMOs)是母乳中的重要成分之一,由于其对新生儿健康的有益作用,引起了极大的关注。由于宿主菌株的可用性、安全性和低成本,已经使用工程微生物途径来大规模生产 HMOs。此外,分子生物学技术和代谢工程的发展促进了 HMOs 生产的有效性。根据目前的报道,已经通过工程微生物途径生产出 2'-岩藻糖基乳糖(2'-FL)、3-岩藻糖基乳糖(3-FL)、乳四糖(LNT)、乳六糖(LNnT)、3'-唾液酸乳糖(3'-SL)、6'-唾液酸乳糖(6'-SL)和一些具有复杂结构的岩藻糖基 HMOs,其中 2'-FL 的产量最高。然而,由于代谢模式的不确定性,宿主菌株的选择具有一定的局限性。除此之外,适当的糖基转移酶在微生物中的表达是合成不同 HMOs 的关键。因此,在使用工程微生物途径时,必须解决寻找安全有效的糖基转移酶的问题。本文综述了利用工程微生物途径生产 HMOs 的最新研究进展。宿主菌株的选择和适应不同的代谢途径有助于研究人员设计更有利于 HMOs 生产的工程微生物途径。

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