Sato Yura, Morishita Yohei, Homma Yuto, Sugawara Akihiro, Moussa Ashaimaa Y, Elissawy Ahmed M, Singab Abdel Nasser B, Ozaki Taro, Asai Teigo
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo 11566, Egypt.
Org Lett. 2025 Jul 4;27(26):7170-7175. doi: 10.1021/acs.orglett.5c02131. Epub 2025 Jun 23.
Circumdatins are a unique class of fungal alkaloids featuring a pyrrolo[4,2]benzodiazepine scaffold. In this study, we identified the biosynthetic gene cluster through genome mining guided by structural analysis and docking simulations. Heterologous expression and precursor feeding experiments revealed an unprecedented tailoring pathway in which anthranilate is modified to yield 5-methoxyanthranilate (5-MA), a substrate for nonribosomal peptide synthetase. This work highlights a unique adenylation domain with substrate promiscuity capable of recognizing both anthranilate and 5-MA.
环蛇菌素是一类独特的真菌生物碱，具有吡咯并[4,2]苯并二氮杂卓骨架。在本研究中，我们通过结构分析和对接模拟引导的基因组挖掘鉴定了生物合成基因簇。异源表达和前体饲喂实验揭示了一条前所未有的修饰途径，其中邻氨基苯甲酸被修饰生成5-甲氧基邻氨基苯甲酸（5-MA），它是非核糖体肽合成酶的一种底物。这项工作突出了一个具有底物选择性的独特腺苷化结构域，该结构域能够识别邻氨基苯甲酸和5-MA。
