赫拉
真菌
菌丝体
立体化学
病原真菌
细胞毒性
抗菌活性
氨基酸
二维核磁共振波谱
生物
生物合成
基因
抗生素
人类病原体
微生物学
化学
细菌
生物化学
体外
遗传学
植物
作者
Dongliang Xiao,Mei Zhang,Ping Wu,Tianyi Li,Wenhua Li,Liwen Zhang,Qiulin Yue,Xinqi Chen,Xiaoyi Wei,Yuquan Xu,Chen Wang
标识
DOI:10.1038/s41429-022-00517-7
摘要
Three new lipopeptaibols, halovirs I-K (1-3), were isolated from the solid culture of the phytopathogenic fungus Paramyrothecium roridum NRRL 2183. Their planar structures, which consist of a hexapeptide backbone and acyl substitutions at the N- and C-termini, were elucidated by comprehensive analysis of the 1D and 2D NMR spectroscopic data along with the detailed interpretation of the MS/MS fragmentation pattern. Absolute configurations of the amino acid/1,2-amino alcohol residues were determined using the advanced Marfey's method. Bioinformatics analysis of the genome assembly of P. roridum NRRL 2183 revealed a gene cluster that is likely responsible for the biosynthesis of halovirs I-K. Analysis of the module and domain organization of the putative halovir synthetase PrHalA indicated that the assembly of 1-3 proceeds in an unconventional nonlinear fashion. 1 and 2 exhibited potent antibacterial activity against both antibiotic-sensitive and multidrug-resistant Gram-positive pathogens. These lipopeptaibols also displayed significant cytotoxicity toward human lung carcinoma A549, human breast carcinoma MCF-7, and human cervical carcinoma HeLa cells with IC50 values ranging from 1.3 to 3.3 μM.
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