利用进化导向的化学合成发现芽孢杆菌科家族革兰氏阴性活性阳离子脂肽抗生素。
Discovery of Paenibacillaceae Family Gram-Negative-Active Cationic Lipopeptide Antibiotics Using Evolution-Guided Chemical Synthesis.
机构信息
Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
出版信息
Org Lett. 2022 Jul 15;24(27):4943-4948. doi: 10.1021/acs.orglett.2c01879. Epub 2022 Jul 1.
Abstract
Cationic nonribosomal lipopeptides (CNRLPs) from spp. have been a rewarding source of Gram-negative-active antibiotics. Here we systematically screened sequenced bacterial genomes for CNRLP biosynthetic gene clusters (BGCs) that we predicted might encode additional Gram-negative-active antibiotics. Total chemical synthesis of the bioinformatically predicted products of seven such BGCs led to our identification of new laterocidine, tridecaptin, and paenibacterin-like antibiotics with potent activity against both multiple-drug-resistant Gram-negative and Gram-positive pathogens.
摘要
来自 spp. 的阳离子非核糖体脂肽 (CNRLP) 一直是革兰氏阴性活性抗生素的丰富来源。在这里，我们系统地对测序细菌基因组进行了筛选，以寻找我们预测可能编码其他革兰氏阴性活性抗生素的 CNRLP 生物合成基因簇 (BGC)。对来自七个 BGC 的生物信息学预测产物进行了全化学合成，这导致我们发现了新的侧霉素、十三肽和巴宾菌素样抗生素，它们对多种耐药革兰氏阴性和革兰氏阳性病原体具有强大的活性。
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