Radical S-Adenosyl Methionine Epimerases: Regioselective Introduction of Diverse D-Amino Acid Patterns into Peptide Natural Products
Radical S-Adenosyl Methionine Epimerases: Regioselective Introduction of Diverse D-Amino Acid Patterns into Peptide Natural Products
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DOI：
10.1002/anie.201400478
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发表时间：
2014-08-04
影响因子：
16.6
通讯作者：
Piel, Joern
中科院分区：
文献类型：
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作者：
Morinaka, Brandon I.;Vagstad, Anna L.;Piel, Joern
PoyD是一种自由基S-腺苷甲硫氨酸差向异构酶，其在交替位置将多个D-构型氨基酸引入高度复杂的海洋肽聚酰氨酰胺A和B中。这种新的翻译后修饰有助于聚茶酰胺形成单分子最小离子通道的能力及其在皮摩尔水平的细胞毒性活性。使用基因组挖掘的方法，我们已经确定了其他的PoyD同系物在各种细菌。在E.大肠杆菌与它们的同源物以及工程肽前体，并显示将不同的D-氨基酸模式引入全-I肽。这些数据揭示了一个家庭的结构和功能不同的酶，表现出高区域选择性，底物混杂，和不可逆的行动，从而提供有吸引力的机会肽工程。
PoyD is a radical S-adenosyl methionine epimerase that introduces multiple D-configured amino acids at alternating positions into the highly complex marine peptides polytheonamide A and B. This novel post-translational modification contributes to the ability of the polytheonamides to form unimolecular minimalistic ion channels and its cytotoxic activity at picomolar levels. Using a genome mining approach we have identified additional PoyD homologues in various bacteria. Three enzymes were expressed in E. coli with their cognate as well as engineered peptide precursors and shown to introduce diverse D-amino acid patterns into all-l peptides. The data reveal a family of architecturally and functionally distinct enzymes that exhibit high regioselectivity, substrate promiscuity, and irreversible action and thus provide attractive opportunities for peptide engineering.