Multi-Omics-Guided Discovery of Omicsynins Produced by Streptomyces sp. 1647: Pseudo-Tetrapeptides Active Against Influenza A Viruses and Coronavirus HCoV-229E.
Multi-Omics-Guided Discovery of Omicsynins Produced by Streptomyces sp. 1647: Pseudo-Tetrapeptides Active Against Influenza A Viruses and Coronavirus HCoV-229E.
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多组学引导下链霉菌产生的组霉素的发现。
DOI：
10.1016/j.eng.2021.05.010
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发表时间：
2022-09
期刊：
影响因子：
--
通讯作者：
Si S
中科院分区：
文献类型：
--
作者：
Sun H;Li X;Chen M;Zhong M;Li Y;Wang K;Du Y;Zhen X;Gao R;Wu Y;Shi Y;Yu L;Che Y;Li Y;Jiang JD;Hong B;Si S
许多微生物都有保护细胞免受病毒攻击的机制。链霉菌发酵成分的研究。1647具有强大的抗甲型流感病毒(IAV)活性。该毒株于20世纪70年代从中国南部的土壤中分离出来，但其抗病毒物质(S)的化学性质至今仍不清楚。我们使用集成的多组学策略来鉴定这种链霉菌中的抗病毒药物。抗生素和次生代谢物分析壳(AntiSMASH)分析其基因组序列，发现38个次生代谢物生物合成基因簇(BGC)，通过生物活性指导的比较转录分析，将可能负责抗病毒成分产生的目标BGC缩小到3个BGC。通过生物信息学分析和对调节子和一个生物合成基因的遗传操作，36簇被鉴定为负责抗病毒化合物生物合成的BGC。基于生物活性的分子网络分析不同重组菌株的光谱数据表明，抗病毒化合物是一类结构类似物。最后，从发酵液中鉴定和/或分离了18个具有内部脲连接的假四肽，即omicsynins A1-A6、B1-B6和C1-C6。其中，11个化合物(omicsynins A1、A2、A6、B1-B3、B5、B6、C1、C2和C6)为新化合物。奥米克辛素B1-B4具有较强的抗病毒活性，其半数抑制浓度(IC_(50))约为1微克分子∙L~(-1)，选择性指数(SI)为100~300。Omicsynins B1-B4对人类冠状病毒HCoV-229E也具有显著的抗病毒活性。通过整合多组学数据，我们发现了一系列新的链霉菌产生的抗病毒伪四肽。1647，表明微生物的次生代谢产物是新型抗病毒药物的宝贵来源。
Many microorganisms have mechanisms that protect cells against attack from viruses. The fermentation components of Streptomyces sp. 1647 exhibit potent anti-influenza A virus (IAV) activity. This strain was isolated from soil in southern China in the 1970s, but the chemical nature of its antiviral substance(s) has remained unknown until now. We used an integrated multi-omics strategy to identify the antiviral agents from this streptomycete. The antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) analysis of its genome sequence revealed 38 biosynthetic gene clusters (BGCs) for secondary metabolites, and the target BGCs possibly responsible for the production of antiviral components were narrowed down to three BGCs by bioactivity-guided comparative transcriptomics analysis. Through bioinformatics analysis and genetic manipulation of the regulators and a biosynthetic gene, cluster 36 was identified as the BGC responsible for the biosynthesis of the antiviral compounds. Bioactivity-based molecular networking analysis of mass spectrometric data from different recombinant strains illustrated that the antiviral compounds were a class of structural analogues. Finally, 18 pseudo-tetrapeptides with an internal ureido linkage, omicsynins A1–A6, B1–B6, and C1–C6, were identified and/or isolated from fermentation broth. Among them, 11 compounds (omicsynins A1, A2, A6, B1–B3, B5, B6, C1, C2, and C6) are new compounds. Omicsynins B1–B4 exhibited potent antiviral activity against IAV with the 50% inhibitory concentration (IC50) of approximately 1 µmol∙L–1 and a selectivity index (SI) ranging from 100 to 300. Omicsynins B1–B4 also showed significant antiviral activity against human coronavirus HCoV-229E. By integrating multi-omics data, we discovered a number of novel antiviral pseudo-tetrapeptides produced by Streptomyces sp. 1647, indicating that the secondary metabolites of microorganisms are a valuable source of novel antivirals.
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影响因子：
2
作者：
HOEBEKE, J;BUSATTOSAMSOEN, C;LEBRUN, E
通讯作者：
LEBRUN, E
影响因子：
7.4
作者：
Fujii, K;Ikai, Y;Harada, K
通讯作者：
Harada, K
影响因子：
4.1
作者：
Lai, Chang-Jiang-Sheng;Zha, Liangping;Huang, Lu-Qi
通讯作者：
Huang, Lu-Qi
影响因子：
15
作者：
Maxson T;Tietz JI;Hudson GA;Guo XR;Tai HC;Mitchell DA
通讯作者：
Mitchell DA
DOI：
10.1007/978-1-60761-987-1_18
发表时间：
2011-01-01
期刊：
DATA MINING IN PROTEOMICS: FROM STANDARDS TO APPLICATIONS
影响因子：
--
作者：
Kohl, Michael;Wiese, Sebastian;Warscheid, Bettina
通讯作者：
Warscheid, Bettina