Kruger Ryan G, Lu Wei, Oberthür Markus, Tao Junhua, Kahne Daniel, Walsh Christopher T
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Chem Biol. 2005 Jan;12(1):131-40. doi: 10.1016/j.chembiol.2004.12.005.
The teicoplanin acyltransferase (Atf) responsible for N-acylation of the glucosamine moiety to create the teicoplanin lipoglycopeptide scaffold has recently been identified. Here we use that enzyme (tAtf) and the cognate acyltransferase from the related A-40,926 biosynthetic cluster (aAtf) to evaluate specificity for glycopeptide scaffolds and for the acyl-CoA donor. In addition to acylation of 2-aminoglucosyl glycopeptide scaffolds with k(cat) values of 400-2000 min(-1), both Atfs transfer acyl groups to regioisomeric 6-aminoglucosyl scaffolds and to glucosyl scaffolds at rates of 0.2-0.5 min(-1) to create variant lipoglycopeptides. Using the teicoplanin glycosyltransferase tGtfA, tAtf, and GtfD, a glycosyltransferase from the vancomycin producer, it is possible to assemble a novel lipoglycopeptide with GlcNAc at beta-OH-Tyr(6) and an N(6)-acyl-glucosaminyl-vancosamine at Phegly(4). This study illustrates the utility of chemo- and regioselective acyltransferases and glycosyltransferases to create novel lipoglycopeptides.
负责对氨基葡萄糖部分进行N - 酰化以生成替考拉宁脂糖肽支架的替考拉宁酰基转移酶（Atf）最近已被鉴定出来。在此，我们使用该酶（tAtf）以及来自相关A - 40,926生物合成簇的同源酰基转移酶（aAtf）来评估对糖肽支架和酰基辅酶A供体的特异性。除了以400 - 2000 min⁻¹的k(cat)值对2 - 氨基葡萄糖基糖肽支架进行酰化外，两种Atf还以0.2 - 0.5 min⁻¹的速率将酰基转移到区域异构体6 - 氨基葡萄糖基支架和葡萄糖基支架上，以生成变体脂糖肽。利用替考拉宁糖基转移酶tGtfA、tAtf以及来自万古霉素产生菌的糖基转移酶GtfD，可以组装一种新型脂糖肽，其在β - OH - Tyr(6)处含有GlcNAc，在Phegly(4)处含有N(6) - 酰基 - 葡萄糖胺基 - 万古糖胺。这项研究说明了化学选择性和区域选择性酰基转移酶及糖基转移酶在创建新型脂糖肽方面的实用性。
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