研究人员发现了一种自然启发的脂肽类抗生素，称为cilagicin，研究人员在对cil生物合成基因簇进行详细的生物信息学分析的基础上，用化学方法合成了它。cilagicin能够封存细胞壁生物合成中使用的两种不同的、不可缺少的十一烯丙基磷酸酯，加上在实验室测试和耐多药的临床分离物中没有检测到耐药性，使它成为打击抗生素耐药性病原体的一个有吸引力的候选物。
据悉，对目前使用的抗生素出现的抗药性是一个全球性的公共卫生危机。由于细菌界中的大部分生物合成能力在以前的抗生素发现工作中保持沉默，在细菌基因组测序研究中发现的未定性的生物合成基因簇，仍然是具有独特作用方式抗生素的一个有吸引力的来源。
附：英文原文
Title: Bioinformatic prospecting and synthesis of a bifunctional lipopeptide antibiotic that evades resistance
Author: Zongqiang Wang, Bimal Koirala, Yozen Hernandez, Matthew Zimmerman, Sean F. Brady
Issue&Volume: 2022-05-27
Abstract: Emerging resistance to currently used antibiotics is a global public health crisis. Because most of the biosynthetic capacity within the bacterial kingdom has remained silent in previous antibiotic discovery efforts, uncharacterized biosynthetic gene clusters found in bacterial genome–sequencing studies remain an appealing source of antibiotics with distinctive modes of action. Here, we report the discovery of a naturally inspired lipopeptide antibiotic called cilagicin, which we chemically synthesized on the basis of a detailed bioinformatic analysis of the cil biosynthetic gene cluster. Cilagicin’s ability to sequester two distinct, indispensable undecaprenyl phosphates used in cell wall biosynthesis, together with the absence of detectable resistance in laboratory tests and among multidrug-resistant clinical isolates, makes it an appealing candidate for combating antibiotic-resistant pathogens.
DOI: abn4213
Source: https://www.science.org/doi/10.1126/science.abn4213