操纵子
基因簇
化学
生物合成
立体化学
基因
生物化学
生物
遗传学
大肠杆菌
作者
Vasiliki T. Chioti,Kenzie A. Clark,Mohammad R. Seyedsayamdost
标识
DOI:10.26434/chemrxiv-2023-b3k7g
摘要
DUF692 multinuclear iron oxygenases (MNIOs) are an emerging family of tailoring enzymes involved in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). Three members, MbnB, TglH, and ChrH, have been characterized to date and shown to catalyze unusual and complex transformations. Using a co-occurrence-based bioinformatic search strategy, we recently generated a sequence similarity network of MNIO-RiPP operons that encode one or more MNIOs adjacent to a transporter. The network revealed >1,000 unique gene clusters, evidence of an unexplored biosynthetic landscape. In this work, we assess an MNIO-RiPP cluster from the network that is encoded in proteobacteria and actinobacteria. The cluster, which we have termed mov (for methanobactin-like operon in Vibrio), encodes a 23-residue precursor peptide, two MNIOs, a RiPP recognition element, and a transporter. Using both in vivo and in vitro methods, we show that one MNIO, homologous to MbnB, installs an oxazolone-thioamide at a Thr-Cys dyad in the precursor. Subsequently, the second MNIO catalyzes N–Cα bond cleavage of the penultimate Asn to generate a C-terminally amidated peptide. This transformation expands the reaction scope of the enzyme family, marks the first ex-ample of an MNIO-catalyzed modification that does not involve Cys, and sets the stage for future exploration of other MNIO-RiPPs
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