Dunlap Walter C, Battershill Christopher N, Liptrot Catherine H, Cobb Rosemary E, Bourne David G, Jaspars Marcel, Long Paul F, Newman David J
Australian Institute of Marine Science, Townsville, Queensland, Australia.
Methods. 2007 Aug;42(4):358-76. doi: 10.1016/j.ymeth.2007.03.001.
Marine invertebrate animals such as sponges, gorgonians, tunicates and bryozoans are sources of biomedicinally relevant natural products, a small but growing number of which are advancing through clinical trials. Most metazoan and anthozoan species harbour commensal microorganisms that include prokaryotic bacteria, cyanobacteria (blue-green algae), eukaryotic microalgae, and fungi within host tissues where they reside as extra- and intra-cellular symbionts. In some sponges these associated microbes may constitute as much as 40% of the holobiont volume. There is now abundant evidence to suggest that a significant portion of the bioactive metabolites thought originally to be products of the source animal are often synthesized by their symbiotic microbiota. Several anti-cancer metabolites from marine sponges that have progressed to pre-clinical or clinical-trial phases, such as discodermolide, halichondrin B and bryostatin 1, are thought to be products derived from their microbiotic consortia. Freshwater and marine cyanobacteria are well recognised for producing numerous and structurally diverse bioactive and cytotoxic secondary metabolites suited to drug discovery. Sea sponges often contain dominant taxa-specific populations of cyanobacteria, and it is these phytosymbionts (= photosymbionts) that are considered to be the true biogenic source of a number of pharmacologically active polyketides and nonribosomally synthesized peptides produced within the sponge. Accordingly, new collections can be pre-screened in the field for the presence of phytobionts and, together with metagenomic screening using degenerate PCR primers to identify key polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes, afford a biodiscovery rationale based on the therapeutic prospects of phytochemical selection. Additionally, new cloning and biosynthetic expression strategies may provide a sustainable method for the supply of new pharmaceuticals derived from the uncultured phytosymbionts of marine organisms.
海绵、柳珊瑚、被囊动物和苔藓虫等海洋无脊椎动物是具有生物医药相关性的天然产物的来源，其中数量虽少但在不断增加的一部分正在进入临床试验阶段。大多数后生动物和珊瑚虫物种体内都有共生微生物，包括原核细菌、蓝细菌（蓝藻）、真核微藻和真菌，它们作为细胞外和细胞内共生体存在于宿主组织中。在一些海绵中，这些相关微生物的体积可能占整个共生体体积的40%。现在有大量证据表明，许多最初被认为是源动物产物的生物活性代谢物实际上往往是由其共生微生物群合成的。几种已进入临床前或临床试验阶段的来自海洋海绵的抗癌代谢物，如盘状软骨素、海兔毒素B和苔藓抑素1，被认为是其微生物群落产生的产物。淡水和海洋蓝细菌因产生众多结构多样、适合药物发现的生物活性和细胞毒性次生代谢物而广为人知。海绵通常含有占主导地位的特定分类群的蓝细菌种群，正是这些植物共生体（=光合共生体）被认为是海绵体内产生的许多具有药理活性的聚酮化合物和非核糖体合成肽的真正生物合成来源。因此，可以在野外对新采集的样本进行植物共生体存在情况的预筛选，并结合使用简并PCR引物进行宏基因组筛选以鉴定关键的聚酮合酶（PKS）和非核糖体肽合成酶（NRPS）基因，从而基于植物化学物质选择的治疗前景提供一种生物发现原理。此外，新的克隆和生物合成表达策略可能为从海洋生物未培养的植物共生体中获取新药物提供一种可持续的方法。
