Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties
Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties
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DOI：
10.1039/b807914e
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发表时间：
2008-09-21
影响因子：
3.2
通讯作者：
Gaisser, Sabine
中科院分区：
文献类型：
--
作者：
Schell, Ursula;Haydock, Stephen F.;Gaisser, Sabine
具有高度修饰的脱氧糖的天然产物支架的糖基化通常是其生物活性所必需的，负责与分子靶点的特定接触并显著影响其药代动力学性质。为了提供有针对性地改变天然产物糖基化模式的工具，在了解活化脱氧糖的生物合成及其转移方面取得了重大进展。我们在这里报道了生产质粒生物合成基因盒的努力，这些基因盒能够生产tdp激活形式的d-肌糖糖、13-氨甘胺和d-去糖胺。我们还描述了利用糖基转移酶EryCIII、TylMII和AngMII将这些脱氧糖转移到大环内酯苷元的过程，这些酶显示出广泛的底物耐受性。
The glycosylation of natural product scaffolds with highly modified deoxysugars is often essential for their biological activity, being responsible for specific contacts to Molecular targets and significantly affecting their pharmacokinetic properties. In order to provide tools for the targeted alteration of natural product glycosylation patterns, significant strides have been made to understand the biosynthesis of activated deoxysugars and their transfer. We report here efforts towards the production of plasmid-borne biosynthetic gene cassettes capable of producing TDP-activated forms of D-mycaminose, 13-angolosamine and D-desosamine. We additionally describe the transfer of these deoxysugars to macrolide aglycones using the glycosyl transferases EryCIII, TylMII and AngMII which display usefully broad substrate tolerance.