Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17649-54. doi: 10.1073/pnas.1108484108. Epub 2011 Oct 10.
Glycosyltransferases are useful synthetic catalysts for generating natural products with sugar moieties. Although several natural product glycosyltransferase structures have been reported, design principles of glycosyltransferase engineering for the generation of glycodiversified natural products has fallen short of its promise, partly due to a lack of understanding of the relationship between structure and function. Here, we report structures of all four calicheamicin glycosyltransferases (CalG1, CalG2, CalG3, and CalG4), whose catalytic functions are clearly regiospecific. Comparison of these four structures reveals a conserved sugar donor binding motif and the principles of acceptor binding region reshaping. Among them, CalG2 possesses a unique catalytic motif for glycosylation of hydroxylamine. Multiple glycosyltransferase structures in a single natural product biosynthetic pathway are a valuable resource for understanding regiospecific reactions and substrate selectivities and will help future glycosyltransferase engineering.
糖基转移酶是生成具有糖基部分的天然产物的有用的合成催化剂。尽管已经报道了几种天然产物糖基转移酶结构，但用于产生糖基多样化天然产物的糖基转移酶工程的设计原则并未如其承诺的那样得到实现，部分原因是缺乏对结构与功能之间关系的理解。在这里，我们报告了所有四种卡拉霉素糖基转移酶（CalG1、CalG2、CalG3 和 CalG4）的结构，它们的催化功能明显具有区域特异性。对这四个结构的比较揭示了一个保守的糖供体结合基序和接受体结合区域重塑的原理。其中，CalG2 具有独特的用于羟胺糖基化的催化基序。单一天然产物生物合成途径中的多个糖基转移酶结构是理解区域特异性反应和底物选择性的宝贵资源，并将有助于未来的糖基转移酶工程。
