基于系统发育学的最小生物合成基因簇产生的新型糖肽抗生素的发现
Phylogeny-Informed Discovery of New Glycopeptide Antibiotics Produced by a Minimal Biosynthetic Gene Cluster.
作者信息
Li Xingkun, Wang Mengru, Yin Lixin, Cao Jiawei, Wang Rui, Guo Wei, Lu Jing, Zhao Zhilong, Deng Zixin, Hou Anwei, Xu Min
机构信息
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West Seventh Avenue, Tianjin 300308, China.
National Technology Innovation Center of Synthetic Biology, 32 West Seventh Avenue, Tianjin 300308, China.
出版信息
Org Lett. 2025 Mar 14;27(10):2444-2449. doi: 10.1021/acs.orglett.5c00378. Epub 2025 Mar 3.
Glycopeptide antibiotics (GPAs) are the frontline medicines to treat multidrug-resistant Gram-positive infections. Resistance to GPAs warrants the development of new antibiotics. Phylogeny reclassification of GPA biosynthetic gene clusters with a focus on the type V subgroup bearing a heptapeptide scaffold identified new GPAs, varsomycins, possessing unprecedented 3,5-dihydroxyphenylalanine at position 5 and an F-G biphenyl cross-link. Varsomycins are broadly active against clinical isolates of methicillin-resistant and vancomycin-resistant and are promising lead compounds for resistance-oriented drug innovation.
糖肽类抗生素（GPA）是治疗多重耐药革兰氏阳性菌感染的一线药物。对GPA产生耐药性促使人们研发新型抗生素。对GPA生物合成基因簇进行系统发育重新分类，重点关注带有七肽支架的V型亚组，从而鉴定出新型GPA——varomycin，其在第5位具有前所未有的3,5-二羟基苯丙氨酸以及F-G联苯交联结构。Varomycin对耐甲氧西林和耐万古霉素的临床分离株具有广泛活性，是面向耐药性的药物创新的有前景的先导化合物。
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