Table_4_Comparative Genomics of Marine Sponge-Derived Streptomyces spp. Isolates SM17 and SM18 With Their Closest Terrestrial Relatives Provides Novel Insights Into Environmental Niche Adaptations and Secondary Metabolite Biosynthesis Potential.DOCX

The emergence of antibiotic resistant microorganisms has led to an increased need for the discovery and development of novel antimicrobial compounds. Frequent rediscovery of the same natural products (NPs) continues to decrease the likelihood of the discovery of new compounds from soil bacteria. Thus, efforts have shifted toward investigating microorganisms and their secondary metabolite biosynthesis potential, from diverse niche environments, such as those isolated from marine sponges. Here we investigated at the genomic level two Streptomyces spp. strains, namely SM17 and SM18, isolated from the marine sponge Haliclona simulans, with previously reported antimicrobial activity against clinically relevant pathogens; using single molecule real-time (SMRT) sequencing. We performed a series of comparative genomic analyses on SM17 and SM18 with their closest terrestrial relatives, namely S. albus J1074 and S. pratensis ATCC 33331 respectively; in an effort to provide further insights into potential environmental niche adaptations (ENAs) of marine sponge-associated Streptomyces, and on how these adaptations might be linked to their secondary metabolite biosynthesis potential. Prediction of secondary metabolite biosynthetic gene clusters (smBGCs) indicated that, even though the marine isolates are closely related to their terrestrial counterparts at a genomic level; they potentially produce different compounds. SM17 and SM18 displayed a better ability to grow in high salinity medium when compared to their terrestrial counterparts, and further analysis of their genomes indicated that they possess a pool of 29 potential ENA genes that are absent in S. albus J1074 and S. pratensis ATCC 33331. This ENA gene pool included functional categories of genes that are likely to be related to niche adaptations and which could be grouped based on potential biological functions such as osmotic stress, defense; transcriptional regulation; symbiotic interactions; antimicrobial compound production and resistance; ABC transporters; together with horizontal gene transfer and defense-related features.

抗生素耐药微生物的出现，使得新型抗菌化合物的发现与开发需求日益迫切。当前，天然产物（natural products, NPs）的重复发现率居高不下，进一步削弱了从土壤细菌中发掘新型抗菌化合物的可行性。为此，研究方向已转向探索来自多样化特殊生境的微生物及其次生代谢物合成潜力，例如分离自海洋海绵的菌株。本研究针对两株分离自海洋海绵Haliclona simulans的链霉菌属（Streptomyces spp.）菌株SM17与SM18展开基因组水平分析：这两株菌株此前已被证实可抑制临床相关病原菌，本研究采用单分子实时（single molecule real-time, SMRT）测序技术对其进行基因组测序。我们以SM17、SM18各自亲缘关系最近的陆生近缘菌株——即分别为S. albus J1074与S. pratensis ATCC 33331——作为参照对象，开展了一系列比较基因组学分析，以期深入阐释海洋海绵共生链霉菌的潜在环境生境适应性（environmental niche adaptations, ENAs），并厘清这类适应性与其次生代谢物合成潜能之间的内在关联。次生代谢物生物合成基因簇（secondary metabolite biosynthetic gene clusters, smBGCs）预测结果显示：尽管这两株海洋分离菌株在基因组层面与其陆生近缘类群亲缘关系紧密，但二者理论上可合成的化合物类型存在显著差异。相较于陆生对照菌株，SM17与SM18在高盐培养基中展现出更优异的生长性能；进一步的基因组分析表明，这两株菌株拥有一套包含29个潜在环境生境适应性基因的基因库，而该基因库在S. albus J1074与S. pratensis ATCC 33331中并未检出。该环境生境适应性基因库涵盖了多个与生境适应相关的功能基因类别，可依据潜在生物学功能划分为：渗透压应激与防御、转录调控、共生互作、抗菌化合物合成与抗性、ABC转运蛋白（ABC transporters），以及水平基因转移（horizontal gene transfer）与防御相关特征等功能群。