Chen Liang-Yu, Cui Hao-Tian, Su Chun, Bai Feng-Wu, Zhao Xin-Qing
State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
School Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, China.
PeerJ. 2019 Jan 3;7:e6122. doi: 10.7717/peerj.6122. eCollection 2019.
Genome sequences of marine streptomycetes are valuable for the discovery of useful enzymes and bioactive compounds by genome mining. However, publicly available complete genome sequences of marine streptomycetes are still limited. Here, we present the complete genome sequence of a marine streptomycete sp. S063 CGMCC 14582. Species delineation based on the pairwise digital DNA-DNA hybridization and genome comparison ANI (average nucleotide identity) value showed that sp. S063 CGMCC 14582 possesses a unique genome that is clearly different from all of the other available genomes. Bioactivity tests showed that sp. S063 CGMCC 14582 produces metabolites with anti-complement activities, which are useful for treatment of numerous diseases that arise from inappropriate activation of the human complement system. Analysis of the genome reveals no biosynthetic gene cluster (BGC) which shows even low similarity to that of the known anti-complement agents was detected in the genome, indicating that sp. S063 CGMCC 14582 may produce novel anti-complement agents of microbial origin. Four BGCs which are potentially involved in biosynthesis of non-ribosomal peptides were disrupted, but no decrease of anti-complement activities was observed, suggesting that these four BGCs are not involved in biosynthesis of the anti-complement agents. In addition, LC-MS/MS analysis and subsequent alignment through the Global Natural Products Social Molecular Networking (GNPS) platform led to the detection of novel peptides produced by the strain. sp. S063 CGMCC 14582 grows rapidly and is salt tolerant, which benefits efficient secondary metabolite production via seawater-based fermentation. Our results indicate that sp. S063 has great potential to produce novel bioactive compounds, and also is a good host for heterologous production of useful secondary metabolites for drug discovery.
海洋链霉菌的基因组序列对于通过基因组挖掘发现有用的酶和生物活性化合物具有重要价值。然而,公开可用的海洋链霉菌完整基因组序列仍然有限。在此,我们展示了一株海洋链霉菌sp. S063 CGMCC 14582的完整基因组序列。基于成对数字DNA-DNA杂交和基因组比较ANI(平均核苷酸同一性)值的物种划分表明,sp. S063 CGMCC 14582拥有独特的基因组,与所有其他可用基因组明显不同。生物活性测试表明,sp. S063 CGMCC 14582产生具有抗补体活性的代谢物,这些代谢物可用于治疗因人类补体系统不适当激活而引发的多种疾病。对基因组的分析表明,在该基因组中未检测到与已知抗补体剂的生物合成基因簇(BGC)具有哪怕很低相似性的基因簇,这表明sp. S063 CGMCC 14582可能产生新型微生物源抗补体剂。四个可能参与非核糖体肽生物合成的BGC被破坏,但未观察到抗补体活性降低,这表明这四个BGC不参与抗补体剂的生物合成。此外,液相色谱-串联质谱(LC-MS/MS)分析以及随后通过全球天然产物社会分子网络(GNPS)平台进行的比对,导致检测到该菌株产生的新型肽。sp. S063 CGMCC 14582生长迅速且耐盐,这有利于通过海水基发酵高效生产次级代谢产物。我们的结果表明,sp. S063具有产生新型生物活性化合物的巨大潜力,并且也是用于药物发现的有用次级代谢产物异源生产的良好宿主。