Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan); Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115 (Taiwan); Graduate Institute of Biotechnology, National Chung-Hsing, University, 250 Kuo Kuang Rd., Taichung 402 (Taiwan); Biotechnology Center, National Chung-Hsing University, 250 Kuo Kuang Rd., Taichung 402 (Taiwan).
Angew Chem Int Ed Engl. 2014 Jul 28;53(31):8060-5. doi: 10.1002/anie.201402313. Epub 2014 Jul 2.
The emergence of antibiotic resistance has prompted active research in the development of antibiotics with new modes of action. Among all essential bacterial proteins, transglycosylase polymerizes lipid II into peptidoglycan and is one of the most favorable targets because of its vital role in peptidoglycan synthesis. Described in this study is a practical enzymatic method for the synthesis of lipid II, coupled with cofactor regeneration, to give the product in a 50-70% yield. This development depends on two key steps: the overexpression of MraY for the synthesis of lipid I and the use of undecaprenol kinase for the preparation of polyprenol phosphates. This method was further applied to the synthesis of lipid II analogues. It was found that MraY and undecaprenol kinase can accept a wide range of lipids containing various lengths and configurations. The activity of lipid II analogues for bacterial transglycolase was also evaluated.
抗生素耐药性的出现促使人们积极研究开发具有新作用模式的抗生素。在所有必需的细菌蛋白中，转糖基酶将脂质 II 聚合到肽聚糖中，由于其在肽聚糖合成中的重要作用，是最有前途的靶标之一。本研究描述了一种实用的酶法合成脂质 II 的方法，该方法与辅因子再生相结合，可使产物的产率达到 50-70%。这一发展依赖于两个关键步骤：过量表达 MraY 用于合成脂质 I 和使用十一烯基磷酸激酶用于制备多萜醇磷酸酯。该方法进一步应用于脂质 II 类似物的合成。研究发现，MraY 和十一烯基磷酸激酶可以接受各种长度和构型的含有各种脂质。还评估了脂质 II 类似物对细菌转糖基酶的活性。
