Identification of the Enzymes Mediating the Maturation of the Seryl‐tRNA Synthetase Inhibitor SB‐217452 during the Biosynthesis of Albomycins

Ushimaru Richiro; Chen Zhang; Zhao Houyuan; Fan Po‐hsun; Liu Hung‐wen

摘要

Abstract > Albomycin δ <sub>2</sub> is a sulfur‐containing sideromycin natural product that shows potent antibacterial activity against clinically important pathogens. The <sc>l</sc> ‐serine‐thioheptose dipeptide partial structure, known as SB‐217452, has been found to be the active seryl‐tRNA synthetase inhibitor component of albomycin δ <sub>2</sub> . Herein, it is demonstrated that AbmF catalyzes condensation between the 6′‐amino‐4′‐thionucleoside with the <sc>d</sc> ‐ ribo configuration and seryl‐adenylate supplied by the serine adenylation activity of AbmK. Formation of the dipeptide is followed by C3′‐epimerization to produce SB‐217452 with the <sc>d</sc> ‐ xylo configuration, which is catalyzed by the radical S ‐adenosyl‐ <sc>l</sc> ‐methionine enzyme AbmJ. Gene deletion suggests that AbmC is involved in peptide assembly linking SB‐217452 with the siderophore moiety. This study establishes how the albomycin biosynthetic machinery generates its antimicrobial component SB‐217452. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 阿尔巴霉素δ. <sub> 2 </ sub> 是含硫的纵横霉素天然产物，其显示对临床重要病原体的有效抗菌活性。这 <sc> l </ sc> 已发现称为Sb-217452的菌丝 - 硫醚二肽部分结构是阿巴莫霉素δ的活性甲基-tRNA合成酶抑制剂组分 <sub> 2 </ sub> 。在此，证明ABMF催化6'-氨基-4'-巯基核苷之间的凝结 <sc> d </ sc> - ribo </ i> ABMK丝氨酸腺苷酸活性提供的构型和甲腺苷酸盐。偶二肽的形成之后是C3 - 缩影，以产生SB-217452 <sc> d </ sc> - XYLO </ I> 配置，由激进催化 s </ i> - 糖基 - <sc> l </ sc> - 甲硫氨酸酶ABMJ。基因缺失表明ABMC参与将SB-217452与纵向部分连接的肽组件。本研究确定了阿尔巴霉素生物合成机械如何产生其抗微生物组分SB-217452。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-19011/'>《Angewandte Chemie》</a> <b style="margin: 0 2px;">|</b><span>2020年第9期</span><b style="margin: 0 2px;">|</b><span>共5页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ushimaru Richiro&option=202" target="_blank" rel="nofollow">Ushimaru Richiro;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Zhang&option=202" target="_blank" rel="nofollow">Chen Zhang;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhao Houyuan&option=202" target="_blank" rel="nofollow">Zhao Houyuan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Fan Po‐hsun&option=202" target="_blank" rel="nofollow">Fan Po‐hsun;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Liu Hung‐wen&option=202" target="_blank" rel="nofollow">Liu Hung‐wen;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Chemistry and Division of Chemical Biology and Medicinal ChemistryUniversity of Texas at AustinAustin TX 78712 USA;</p> <p>Department of Chemistry and Division of Chemical Biology and Medicinal ChemistryUniversity of Texas at AustinAustin TX 78712 USA;</p> <p>Department of Chemistry and Division of Chemical Biology and Medicinal ChemistryUniversity of Texas at AustinAustin TX 78712 USA;</p> <p>Department of Chemistry and Division of Chemical Biology and Medicinal ChemistryUniversity of Texas at AustinAustin TX 78712 USA;</p> <p>Department of Chemistry and Division of Chemical Biology and Medicinal ChemistryUniversity of Texas at AustinAustin TX 78712 USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1188.html" title="应用化学">应用化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=albomycin&option=203" rel="nofollow">albomycin;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=amide bond formation&option=203" rel="nofollow">amide bond formation;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=biosynthesis&option=203" rel="nofollow">biosynthesis;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=epimerization&option=203" rel="nofollow">epimerization;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=radical S-adenosyl-l-methionine enzymes&option=203" rel="nofollow">radical S-adenosyl-l-methionine enzymes;</a> </p> <div class="translation"> 机译：氨基霉素;酰胺键形成;生物合成;缩写;基团S-腺苷-1-蛋氨酸酶; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" 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