Institute of Medical Sciences, University of Aberdeen Ashgrove Road West, Aberdeen, AB25 2ZD, UK.
Department of Chemistry, University of Aberdeen, Aberdeen, AB24 3UE, UK.
Angew Chem Int Ed Engl. 2023 Apr 11;62(16):e202215979. doi: 10.1002/anie.202215979. Epub 2023 Mar 10.
Aromatic prenyltransferases from cyanobactin biosynthetic pathways catalyse the chemoselective and regioselective intramolecular transfer of prenyl/geranyl groups from isoprene donors to an electron-rich position in these macrocyclic and linear peptides. These enzymes often demonstrate relaxed substrate specificity and are considered useful biocatalysts for structural diversification of peptides. Herein, we assess the isoprene donor specificity of the N1-tryptophan prenyltransferase AcyF from the anacyclamide A8P pathway using a library of 22 synthetic alkyl pyrophosphate analogues, of which many display reactive groups that are amenable to additional functionalization. We further used AcyF to introduce a reactive moiety into a tryptophan-containing cyclic peptide and subsequently used click chemistry to fluorescently label the enzymatically modified peptide. This chemoenzymatic strategy allows late-stage modification of peptides and is useful for many applications.
芳基 prenyltransferases 来自 cyanobactin 生物合成途径，催化从异戊二烯供体到这些大环和线性肽中电子富位的化学选择性和区域选择性的 prenyl/geranyl 基团的内分子转移。这些酶通常表现出宽松的底物特异性，被认为是用于肽结构多样化的有用的生物催化剂。在此，我们使用 22 种合成的烷基焦磷酸酯类似物的文库评估来自 anacyclamide A8P 途径的 N1-色氨酸 prenyltransferase AcyF 的异戊二烯供体特异性，其中许多显示出可进一步官能化的反应性基团。我们进一步使用 AcyF 将反应性部分引入含色氨酸的环状肽中，然后使用点击化学将酶修饰的肽荧光标记。这种化学酶策略允许肽的后期修饰，并且对于许多应用非常有用。
