N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway
N-Prenylation of Tryptophan by an Aromatic Prenyltransferase from the Cyanobactin Biosynthetic Pathway
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DOI：
10.1021/acs.biochem.8b00879
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发表时间：
2018-12-18
期刊：
影响因子：
2.9
通讯作者：
Fewer, David P.
中科院分区：
文献类型：
--
作者：
Dalponte, Luca;Parajuli, Anirudra;Fewer, David P.
芳香族预烯基化是许多天然产物生物合成的重要步骤，并导致化学结构的惊人多样性。氰基肌动蛋白途径经常编码芳香族戊烯基转移酶，催化这些大环和线状多肽的戊烯基化。在这里，我们鉴定了鱼腥藻(Anabaena sp.)的异烟肼(Acy)生物合成基因簇。UHC-0232。ACY途径的部分重组、异源表达和体外生化特性表明，编码在ACY生物合成基因簇中的ACYF酶是一种Trp N-戊烯基转移酶。生物信息学分析表明，在异戊烯基化的天然产物中，氰基酪氨酸戊烯转移酶的单一来源和快速多样化，以及N-1色氨酸戊烯基化的多重来源。ACYF酶对一系列含有色氨酸的底物表现出高度的柔韧性，代表了一种有趣的生物催化应用的新工具。
Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression, and in vitro biochemical characterization demonstrate that the AcyF enzyme, encoded in the acy biosynthetic gene cluster, is a Trp N-prenyltransferase. Bioinformatic analysis suggests the monophyletic origin and rapid diversification of cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility toward a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.