Stereospecific prenylation of tryptophan by a cyanobacterial post-translational modification enzyme
Stereospecific prenylation of tryptophan by a cyanobacterial post-translational modification enzyme
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DOI：
10.1039/c6ob01759b
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发表时间：
2016-10-28
影响因子：
3.2
通讯作者：
Abe, Ikuro
中科院分区：
文献类型：
--
作者：
Okada, Masahiro;Sugita, Tomotoshi;Abe, Ikuro
异戊二烯化是增加肽和蛋白质的结构多样性和生物活性的关键翻译后反应。迄今为止，仅鉴定出一种翻译后修饰酶 ComQ 可以介导核糖体合成肽中色氨酸残基的异戊二烯化。在此，我们报告了 KgpF 的体外表征，KgpF 是一种新型异戊烯基转移酶，可在 kawaguchipeptin A 生物合成过程中将二甲基烯丙基部分转移至色氨酸残基。 KgpF 的立体特异性异戊二烯化通过 KgpF 对 Fmoc-色氨酸的体外二甲基烯丙基化和二甲基烯丙基化的 Fmoc-色氨酸非对映体的化学合成相结合来确定。 KgpF 在色氨酸衍生物的吲哚环 3 位处用二甲基烯丙基修饰，形成三环结构，其支架与 ComQ 异戊二烯化相同，但立体化学相反。
Prenylation is a key post-translational reaction to increase the structural diversity and bioactivity of peptides and proteins. Until now, only one post-translational modification enzyme, ComQ, has been identified to mediate the prenylation of a tryptophan residue in ribosomally synthesized peptides. Here, we report the in vitro characterization of KgpF, a novel prenyltransferase which transfers dimethylallyl moieties to tryptophan residues during kawaguchipeptin A biosynthesis. The stereospecific prenylation by KgpF was determined by a combination of in vitro dimethylallylation of Fmoc-tryptophan by KgpF and chemical synthesis of dimethylallylated Fmoc-tryptophan diastereomers. KgpF modified the tryptophan derivative with a dimethylallyl group at the 3 position of its indole ring, resulting in the formation of a tricyclic structure with the same scaffold as prenylation by ComQ, but with the opposite stereochemistry.