Department of Pharmacy, National University of Singapore, Singapore 117544, Singapore.
ACS Chem Biol. 2022 Dec 16;17(12):3284-3289. doi: 10.1021/acschembio.2c00621. Epub 2022 Dec 1.
Triceptides are ribosomally synthesized and post-translationally modified peptides characterized by three-residue cyclophanes. The cyclophanes are installed by radical SAM/SPASM maturases referred to as 3-residue cyclophane forming enzymes (3-CyFEs) which catalyze C()-Cβ() bond formation on three residue motifs at the C-terminus of precursor peptides. Here, we bioinformatically map uncharacterized rSAM/SPASM enzymes, referred to as Actinobacterial multiple cyclophane maturases. The enzyme FwwB from was selected for functional studies in , and was found to catalyze formation of multiple Phe- and Trp-derived 3-residue cyclophanes. FwwB was shown to accept a series of engineered substrates but showed specificity for the native 3-residue motif.
三肽是通过核糖体合成和翻译后修饰的肽，其特征是含有三个残基的环丙烷。环丙烷是由自由基 SAM/SPASM 成熟酶（称为 3 残基环丙烷形成酶（3-CyFEs））安装的，它们催化前体肽 C 末端三个残基基序上的 C()-Cβ()键形成。在这里，我们通过生物信息学方法对未表征的 rSAM/SPASM 酶进行了映射，称为放线菌多环烷成熟酶。从 中选择了酶 FwwB 进行 在 中的功能研究，并发现它能够催化形成多个苯丙氨酸和色氨酸衍生的 3 残基环丙烷。FwwB 被证明可以接受一系列工程化的底物，但对天然的 3 残基基序具有特异性。
