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Abstract：
BACKGROUND: A growing number of studies have demonstrated that the polar regions have the potential to be a significant repository of microbial resources and a potential source of active ingredients. Genome mining strategy plays a key role in the discovery of bioactive secondary metabolites (SMs) from microorganisms. This work highlighted deciphering the biosynthetic potential of an Arctic marine-derived strain Aspergillus sydowii MNP-2 by a combination of whole genome analysis and antiSMASH as well as feature-based molecular networking (MN) in the Global Natural Products Social Molecular Networking (GNPS).
RESULTS: In this study, a high-quality whole genome sequence of an Arctic marine strain MNP-2, with a size of 34.9 Mb was successfully obtained. Its total number of genes predicted by BRAKER software was 13,218, and that of non-coding RNAs (rRNA, sRNA, snRNA, and tRNA) predicted by using INFERNAL software was 204. AntiSMASH results indicated that strain MNP-2 harbors 56 biosynthetic gene clusters (BGCs), including 18 NRPS/NRPS-like gene clusters, 10 PKS/PKS-like gene clusters, 8 terpene synthse gene clusters, 5 indole synthase gene clusters, 10 hybrid gene clusters, and 5 fungal-RiPP gene clusters. Metabolic analyses of strain MNP-2 grown on various media using GNPS networking revealed its great potential for the biosynthesis of bioactive SMs containing a variety of heterocyclic and bridge-ring structures. For example, compound G-8 exhibited a potent anti-HIV effect with an IC50 value of 7.2 nM and an EC50 value of 0.9 nM. Compound G-6 had excellent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U1975, SGC-7901, A549, MOLT-4, and HL60 cell lines, with IC50 values ranging from 0.10 to 3.3 µM, and showed significant anti-viral (H1N1 and H3N2) activities with IC50 values of 15.9 and 30.0 µM, respectively.
CONCLUSIONS: These findings definitely improve our knowledge about the molecular biology of genus A. sydowii and would effectively unveil the biosynthetic potential of strain MNP-2 using genomics and metabolomics techniques.
RESULTS: In this study, a high-quality whole genome sequence of an Arctic marine strain MNP-2, with a size of 34.9 Mb was successfully obtained. Its total number of genes predicted by BRAKER software was 13,218, and that of non-coding RNAs (rRNA, sRNA, snRNA, and tRNA) predicted by using INFERNAL software was 204. AntiSMASH results indicated that strain MNP-2 harbors 56 biosynthetic gene clusters (BGCs), including 18 NRPS/NRPS-like gene clusters, 10 PKS/PKS-like gene clusters, 8 terpene synthse gene clusters, 5 indole synthase gene clusters, 10 hybrid gene clusters, and 5 fungal-RiPP gene clusters. Metabolic analyses of strain MNP-2 grown on various media using GNPS networking revealed its great potential for the biosynthesis of bioactive SMs containing a variety of heterocyclic and bridge-ring structures. For example, compound G-8 exhibited a potent anti-HIV effect with an IC50 value of 7.2 nM and an EC50 value of 0.9 nM. Compound G-6 had excellent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U1975, SGC-7901, A549, MOLT-4, and HL60 cell lines, with IC50 values ranging from 0.10 to 3.3 µM, and showed significant anti-viral (H1N1 and H3N2) activities with IC50 values of 15.9 and 30.0 µM, respectively.
CONCLUSIONS: These findings definitely improve our knowledge about the molecular biology of genus A. sydowii and would effectively unveil the biosynthetic potential of strain MNP-2 using genomics and metabolomics techniques.
摘要：
背景：越来越多的研究表明，极地地区有可能成为微生物资源的重要储存库和活性成分的潜在来源。基因组挖掘策略在从微生物中发现生物活性次级代谢产物（SMs）中起着关键作用。这项工作强调了通过全基因组分析和抗SMASH以及全球天然产物社会分子网络（GNPS）中基于特征的分子网络（MN）的组合来破译北极海洋衍生菌株sydowiiMNP-2的生物合成潜力。
结果：在这项研究中，成功获得了大小为34.9Mb的北极海洋菌株MNP-2的高质量全基因组序列。BRAKER软件预测的基因总数为13,218，非编码RNA（rRNA，sRNA,snRNA,使用INFERNAL软件预测的tRNA）为204。AntiSMASH结果表明，菌株MNP-2具有56个生物合成基因簇（BGC），包括18个NRPS/NRPS样基因簇，10个PKS/PKS样基因簇，8个萜烯合成基因簇，5吲哚合酶基因簇，10个杂种基因簇，和5个真菌-RiPP基因簇。使用GNPS网络在各种培养基上生长的菌株MNP-2的代谢分析显示，其在生物合成包含多种杂环和桥环结构的生物活性SM方面具有巨大潜力。例如,化合物G-8表现出有效的抗HIV作用,IC50值为7.2nM,EC50值为0.9nM。化合物G-6对K562、MCF-7、Hela、DU145，U1975，SGC-7901，A549，MOLT-4和HL60细胞系，IC50值范围为0.10至3.3µM，并显示出显著的抗病毒（H1N1和H3N2）活性，IC50值为15.9和30.0µM，分别。
结论：这些发现肯定会提高我们对A.sydowii属分子生物学的认识，并将使用基因组学和代谢组学技术有效揭示菌株MNP-2的生物合成潜力。
结果：在这项研究中，成功获得了大小为34.9Mb的北极海洋菌株MNP-2的高质量全基因组序列。BRAKER软件预测的基因总数为13,218，非编码RNA（rRNA，sRNA,snRNA,使用INFERNAL软件预测的tRNA）为204。AntiSMASH结果表明，菌株MNP-2具有56个生物合成基因簇（BGC），包括18个NRPS/NRPS样基因簇，10个PKS/PKS样基因簇，8个萜烯合成基因簇，5吲哚合酶基因簇，10个杂种基因簇，和5个真菌-RiPP基因簇。使用GNPS网络在各种培养基上生长的菌株MNP-2的代谢分析显示，其在生物合成包含多种杂环和桥环结构的生物活性SM方面具有巨大潜力。例如,化合物G-8表现出有效的抗HIV作用,IC50值为7.2nM,EC50值为0.9nM。化合物G-6对K562、MCF-7、Hela、DU145，U1975，SGC-7901，A549，MOLT-4和HL60细胞系，IC50值范围为0.10至3.3µM，并显示出显著的抗病毒（H1N1和H3N2）活性，IC50值为15.9和30.0µM，分别。
结论：这些发现肯定会提高我们对A.sydowii属分子生物学的认识，并将使用基因组学和代谢组学技术有效揭示菌株MNP-2的生物合成潜力。
