Structural Revision of Natural Cyclic Depsipeptide MA026 Established by Total Synthesis and Biosynthetic Gene Cluster Analysis
Structural Revision of Natural Cyclic Depsipeptide MA026 Established by Total Synthesis and Biosynthetic Gene Cluster Analysis
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全合成和生物合成基因簇分析建立的天然环缩酚肽MA026的结构修饰
DOI：
10.1002/anie.202015193
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hayashi Yoshi
中科院分区：
文献类型：
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作者：
Uchiyama Chihiro;Fukuda Akane;Mukaiyama Minagi;Nakazawa Yoshiki;Kuramochi Yuka;Muguruma Kyohei;Arimoto Mitsue;Ninomiya Akihiro;Kako Koichiro;Katsuyama Yohei;Konno Sho;Taguchi Akihiro;Takayama Kentaro;Taniguchi Atsuhiko;Nagumo Yoko;Usui Takeo;Hayashi Yoshi
天然14-mer环状缩酚酸肽MA 026的修订结构，分离自假单胞菌属。RtlB 026于2002年通过HPLC、MS/MS和NMR的理化分析建立，并通过全固相合成进行确认。修订后的结构不同于以前报道的两个氨基酸残基，分配错误，已被替换。在基于细胞的紧密连接（TJ）开放测定中，具有修改结构的合成的MA 026显示出与天然的紧密连接（TJ）开放活性相似的紧密连接（TJ）开放活性。对RtIB 026的推定MA 026生物合成基因簇（BGC）的生物信息学分析表明，修正结构中每个氨基酸残基的立体化学可以合理地解释。与黄溶血素BGC的系统发育分析表明异常高的同源性（约。90%）。MA 026与claudin-1结合时的TJ开放活性是大亲水性生物制剂经皮给药新途径的关键。
A revised structure of natural 14‐mer cyclic depsipeptide MA026, isolated fromPseudomonassp. RtlB026 in 2002 was established by physicochemical analysis with HPLC, MS/MS, and NMR and confirmed by total solid‐phase synthesis. The revised structure differs from that previously reported in that two amino acid residues, assigned in error, have been replaced. Synthesized MA026 with the revised structure showed a tight junction (TJ) opening activity like that of the natural one in a cell‐based TJ opening assay. Bioinformatic analysis of the putative MA026 biosynthetic gene cluster (BGC) of RtIB026 demonstrated that the stereochemistry of each amino acid residue in the revised structure can be reasonably explained. Phylogenetic analysis with xantholysin BGC indicates an exceptionally high homology (ca. 90 %) between xantholysin and MA026. The TJ opening activity of MA026 when binding to claudin‐1 is a key to new avenues for transdermal administration of large hydrophilic biologics.