Biomedical Sciences Research Complex, University of St Andrews, St Andrews, UK.
Nat Struct Mol Biol. 2012 Aug;19(8):767-72. doi: 10.1038/nsmb.2340. Epub 2012 Jul 15.
Peptide macrocycles are found in many biologically active natural products. Their versatility, resistance to proteolysis and ability to traverse membranes has made them desirable molecules. Although technologies exist to synthesize such compounds, the full extent of diversity found among natural macrocycles has yet to be achieved synthetically. Cyanobactins are ribosomal peptide macrocycles encompassing an extraordinarily diverse range of ring sizes, amino acids and chemical modifications. We report the structure, biochemical characterization and initial engineering of the PatG macrocyclase domain of Prochloron sp. from the patellamide pathway that catalyzes the macrocyclization of linear peptides. The enzyme contains insertions in the subtilisin fold to allow it to recognize a three-residue signature, bind substrate in a preorganized and unusual conformation, shield an acyl-enzyme intermediate from water and catalyze peptide bond formation. The ability to macrocyclize a broad range of nonactivated substrates has wide biotechnology applications.
肽大环化合物存在于许多具有生物活性的天然产物中。它们的多功能性、抗蛋白水解能力和跨膜能力使它们成为理想的分子。尽管已经有技术可以合成这些化合物，但天然大环化合物的多样性尚未在合成上完全实现。蓝细菌肽大环化合物包含了极其多样的环大小、氨基酸和化学修饰。我们报告了来自 patellamide 途径的 Prochloron sp. 的 PatG 环化酶结构域的结构、生化特性和初步工程设计，该酶催化线性肽的环化。该酶在枯草杆菌蛋白酶折叠中有插入，使其能够识别三残基特征，以预组织和不寻常的构象结合底物，将酰基-酶中间体与水隔离，并催化肽键形成。能够大环化广泛的非活化底物具有广泛的生物技术应用。
