The thioesterase domain of the fengycin biosynthesis cluster: A structural base for the macrocyclization of a non-ribosomal lipopeptide
The thioesterase domain of the fengycin biosynthesis cluster: A structural base for the macrocyclization of a non-ribosomal lipopeptide
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DOI：
10.1016/j.jmb.2006.03.062
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发表时间：
2006-06-16
影响因子：
5.6
通讯作者：
Essen, Lars-Oliver
中科院分区：
文献类型：
--
作者：
Samel, Stefan A.;Wagner, Bjoern;Essen, Lars-Oliver
来自细菌和真菌的许多次级代谢肽由非核糖体肽合成酶（NRPS）产生，其中生物合成的最后步骤通常由指定的硫酯酶结构域催化。在这里，我们报告了枯草芽孢杆菌F29-3的芬枯草菌素硫酯酶（FenTE）的1.8埃晶体结构，该硫酯酶催化抗生素芬枯草菌素从NRPS模板的区域和立体选择性释放和大环化。PMSF失活的FenTE结构域的结构表明氧阴离子孔的位置和脂肽的C-末端残基L-Ile 11的结合位点。使用对接，分子动力学模拟和体外活性测定的组合，FenTE-芬枯草菌素复合物的模型，其中肽环化需要与内衬活性位点峡谷的残基的战略相互作用。(c)2006爱思唯尔有限公司保留所有权利。
Many secondary metabolic peptides from bacteria and fungi are produced by non-ribosomal peptide synthetases (NRPS) where the final step of biosynthesis is often catalysed by designated thioesterase domains. Here, we report the 1.8 angstrom crystal structure of the fengycin thioesterase (FenTE) from Bacillus subtilis F29-3, which catalyses the regio- and stereoselective release and macrocyclization of the antibiotic fengycin from the NRPS template. A structure of the PMSF-inactivated FenTE domain suggests the location of the oxyanion hole and the binding site of the C-terminal residue L-Ile11 of the lipopeptide. Using a combination of docking, molecular dynamics simulations and in vitro activity assays, a model of the FenTE-fengycin complex was derived in which peptide cyclization requires strategic interactions with residues lining the active site canyon. (c) 2006 Elsevier Ltd. All rights reserved.