Heterologous expression of a cryptic gene cluster from Grimontia marina affords a novel tricyclic peptide grimoviridin
Heterologous expression of a cryptic gene cluster from Grimontia marina affords a novel tricyclic peptide grimoviridin
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DOI：
10.1007/s00253-020-10605-z
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发表时间：
2020-04
影响因子：
5
通讯作者：
Kohta Unno;Issara Kaweewan;H. Nakagawa;S. Kodani
中科院分区：
文献类型：
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作者：
Kohta Unno;Issara Kaweewan;H. Nakagawa;S. Kodani
摘要微病毒素是一类由核糖体合成并经酶解后修饰的多肽，广泛存在于蓝藻中。在变形菌门和拟杆菌门的细菌基因组中存在相似的RIPPs基因簇。在海洋γ-变形杆菌Grimontia marina的基因组中发现了一个微绿素型肽的隐藏基因簇，利用该基因簇在大肠杆菌中异源合成了一种新的微绿素型肽grimoviridin。通过MS和NMR数据分析确定了grimoviridin的结构。Grimoviridin含有一个异肽和两个酯键，其具有与其他microviridin型肽完全相同的桥接模式。用改良的马氏法测定了组成氨基酸的绝对立体化学均为L型。Grimoviridin对胰蛋白酶显示出有效的抑制活性，IC 50值为238 nM。这是首次报道使用来自变形杆菌的生物合成基因簇异源生产microviridin型肽。关键点·异源生产提供了新的microviridin型肽，命名为grimoviridin。·这是首次报道来自变形菌的microviridin型肽。·Grimoviridin对胰蛋白酶显示出有效的抑制活性。
AbstractMicroviridins are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that have been isolated from a wide variety of cyanobacterial strains. There are similar gene clusters of RiPPs distributed in the genomes of bacteria belonging to the phylaProteobacteriaandBacteroidetes. A cryptic gene cluster for the production of microviridin-type peptide was found in the genome of the marine γ-Proteobacterium Grimontia marina.Heterologous production of new microviridin-type peptide named grimoviridin was accomplished inEscherichia coliusing the biosynthetic gene cluster ofG. marina.The structure of grimoviridin was determined by analysis of MS and NMR data. Grimoviridin contained one isopeptide and two ester bonds, which had exactly the same bridging pattern as other microviridin-type peptides. The absolute stereochemistries of constituent amino acids were determined to be all L-forms by modified Marfey’s method. Grimoviridin showed potent inhibitory activity against trypsin with an IC50value of 238 nM. This is the first report of heterologous production of microviridin-type peptide using a biosynthetic gene cluster from aProteobacterium.Key points• Heterologous production afforded new microviridin-type peptide named grimoviridin.• This is the first report of microviridin-type peptide from proteobacterial origin.• Grimoviridin showed potent inhibitory activity against trypsin.