General Tolerance of Galactosyltransferases toward UDP-galactosamine Expands Their Synthetic Capability.

General Tolerance of Galactosyltransferases toward UDP-galactosamine Expands Their Synthetic Capability.
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DOI:
10.1002/anie.202112574
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发表时间:
2021-12-13
期刊:
Angewandte Chemie (International ed. in English)
影响因子:
--
通讯作者:
Li L
Li L
中科院分区:
其他
文献类型:
--
作者:
Fu X;Gadi MR;Wang S;Han J;Liu D;Chen X;Yin J;Li L

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大量结构多样的聚糖及其衍生物是功能性糖组学所必需的。我们显示了半乳糖基转移酶对尿苷二磷酸半乳糖胺(UDP-GalN)的一般耐受性,尿苷二磷酸半乳糖胺不是常用的糖核苷酸供体。利用该特性开发了两步化学酶促策略,用于在制备规模中容易地合成新颖和发散的N-乙酰半乳糖胺(GalNAc)-糖苷和衍生物。现有糖基转移酶的新特性的发现和应用扩展了它们在产生新型糖键方面的催化能力,从而促进了用于生物学研究的各种聚糖和糖缀合物的合成。制备不同的聚糖是糖生物学所必需的,而用于此目的的合成有用的酶是有限的。本研究发现半乳糖基转移酶(GalTs)对罕见供体UDP-半乳糖胺的一般耐受性。设计了两步策略来利用这种性质来容易地合成GalNAc-糖苷。新发现的半乳糖苷酶的催化特性将大大扩展其在化学糖生物学中的应用。
Accessing large numbers of structurally diverse glycans and derivatives is essential to functional glycomics. We showed a general tolerance of galactosyltransferases toward uridine-diphosphate-galactosamine (UDP-GalN), which is not a commonly used sugar nucleotide donor. The property was harnessed to develop a two-step chemoenzymatic strategy for facile synthesis of novel and divergent N-acetylgalactosamine (GalNAc)-glycosides and derivatives in preparative scales. The discovery and the application of the new property of existing glycosyltransferases expand their catalytic capabilities in generating novel carbohydrate linkages, thus prompting the synthesis of diverse glycans and glycoconjugates for biological studies. Preparation of diverse glycans is essential to glycobiology, while synthetic-useful enzymes for this purpose are limited. This study discovered a general tolerance of galactosyltransferases (GalTs) toward uncommon donor UDP-galactosamine. A two-step strategy was devised to harness this property for the facile synthesis of GalNAc-glycosides. The newly identified catalytic properties of GalTs would greatly expand their utilization in chemical glycobiology.
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