Modern organic chemistry faces many difficulties in the reliable production of cyclopeptides, such as poor yields and insufficient regio- and stereoselectivity. Thioesterase (TE) shows impressive stereospecificity, region- and chemoselectivity during the cyclization of peptide substrates. The biocatalytic properties of TE provide high value for industrial applications. Herein, a novel chemoenzymatic method to synthesize cilengitide is described based on the cyclic activity of the TE domain from microcystin synthetase C (McyC) of Microcystis aeruginosa. In addition, a single active site mutation in the McyC TE was engineered to generate a more effective macrocyclization catalyst. Compared to the chemical approach to synthesize cilengitide, this novel enzyme-catalysed methodology exhibits a higher synthetic efficiency with an approximately 3.4-fold higher yield (49.2%).

中文翻译：

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一种使用铜绿微囊藻微囊藻毒素合成酶C的硫酯酶结构域生产Cilengitide的新型化学酶法。

现代有机化学在可靠生产环肽方面面临许多困难，例如收率低以及区域和立体选择性不足。硫酯酶（TE）在肽底物环化过程中显示出令人印象深刻的立体特异性，区域选择性和化学选择性。TE的生物催化性能为工业应用提供了很高的价值。在此，基于铜绿微囊藻的微囊藻毒素合成酶C（McyC）的TE结构域的循环活性，描述了合成西仑肽的新型化学酶法。另外，对McyC TE中的单个活性位点突变进行了工程改造，以生成更有效的大环化催化剂。与化学方法合成西仑吉肽相比，这种新颖的酶催化方法显示出更高的合成效率，产率约高3.4倍（49.2％）。