Enzymatic Synthesis of Human Milk Fucosides α1,2-Fucosyl para-Lacto-N-Hexaose and its Isomeric Derivatives

Enzymatic Synthesis of Human Milk Fucosides α1,2-Fucosyl para-Lacto-N-Hexaose and its Isomeric Derivatives
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DOI:
10.1002/adsc.201800518
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发表时间:
2018-09-03
影响因子:
5.4
通讯作者:
Yu, Ching-Ching
Yu, Ching-Ching
中科院分区:
化学2区
文献类型:
--
作者:
Fang, Jia-Lin;Tsai, Teng-Wei;Yu, Ching-Ching

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使用连续一锅酶系统实现对-乳糖-N-六糖及其异构体结构以及人乳低聚糖(HMO)中天然存在的那些α 1,2-岩藻糖基化变体的酶促合成。开发了三种糖基化途径,包括细菌糖基转移酶和相应的糖核苷酸生成酶,以促进有效生产延长的1型和2型N-乙酰乳糖胺(LacNAc)主链和杂合链。进一步研究了两种α 1,2-岩藻糖基转移酶在六糖的1型和2型链上的岩藻糖基化效率,以实现岩藻糖基化聚糖的实际合成。结构确定的HMO的可用性为研究未来的生物应用提供了一种实用的方法。
Enzymatic synthesis of para-lacto-N-hexaose and its isomeric structures as well as those alpha 1,2-fucosylated variants naturally occurring in human milk oligosaccharide (HMOs) was achieved using a sequential one-pot enzymatic system. Three glycosylation routes comprising bacterial glycosyl-transferases and corresponding sugar-nucleotide-generating enzymes were developed to facilitate efficient production of extended type-1 and type-2N-acetyllactosamine (LacNAc) backbones and hybrid chains. Further fucosylation efficiency of two alpha 1,2-fucosyltransferases on both type-1 and type-2 chains of the hexasaccharide was investigated to achieve practical synthesis of the fucosylated glycans. The availability of structurally defined HMOs offers a practical approach for investigating future biological applications.