Biomedicinals from the phytosymbionts of marine invertebrates: a molecular approach

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.     

海洋微生物及海藻抗HIV天然产物研究进展

艾滋病是当今重大的公共卫生问题和社会问题。从天然资源寻找新抗HIV活性天然产物是新药发现的重要途径。综述了来源于海洋微生物、海藻具抗HIV活性的天然产物以及抗H1V活性天然产物筛选方法和靶点。     

海洋动植物共附生微生物的分离和抗菌活性研究

从海参、海胆、海葵、海兔、石莼、羊栖菜、裙带菜分离得到125种共附生海洋微生物,以6种敏感菌为指示菌,从中获得具有抑菌活性的细菌21株,放线菌8株,真菌2株。21株抑菌海洋细菌中芽孢杆菌属为7株,占33．3％,弧菌属为11种,占52．2％,其余3株为假单孢杆菌属,占14．5％。8株抑菌海洋放线菌中链霉菌属为5株,占62．5％,小单孢菌属为3株,占36．5％。2株抑菌海洋真菌均为青霉属。     

Organ-specific distribution of dietary alkaloids in the marine opisthobranch Tylodina perversa

Specimens of the opisthobranch Tylodina perversa that were observed while feeding on the sponge Aplysina aerophoba were transferred to seawater tanks along with their prey and kept under controlled conditions. After one week the opisthobranchs were anaesthetized, dissected and studied for sequestered sponge-derived brominated alkaloids. All parts of T. perversa analyzed including feces, mucus and egg masses that had been produced during captivity contained alkaloids derived from A. aerophoba. The highest total alkaloid concentration (24.6 mg g⁻¹ dry wt) was found in mantles of T. perversa (compared to 51.2 mg g⁻¹ dry wt of total alkaloids in A. aerophoba). Hepatopancreas, egg masses and mucus (respective total alkaloid concentrations ranging from 20.4 to 12.5 mg g⁻¹ dry wt) were also rich in alkaloids. Whereas in A. aerophoba the isoxazoline alkaloids aerophobin-2 and isofistularin-3 were present in almost equal concentrations, aerophobin-2 constituted by far the major alkaloid (amounting to approximately 70% of all identified alkaloids) in mantles, mucus and egg masses of T. perversa, indicating selective sequestration by the opisthobranchs. Mantles as well as mucus also contained appreciable concentrations (approximately 20% of all identified compounds) of the brominated alkaloid aerothionin; this is not detected in A. aerophoba. It is possible that aerothionin originates from a previous encounter of T. perversa with the sponge A. cavernicola, the latter being closely related to A. aerophoba. The enrichment of aerophobin-2 (and of aerothionin) in mantles, mucus and egg masses that are vulnerable and exposed (mantles and egg masses) to predators and/or pathogens argues for defensive functions of the respective alkaloids even though this hypothesis still needs to be experimentally corroborated.     

Tokaramide A,a new cathepsin B inhibitor from the marine sponge Theonella aff. mirabilis

A new cathepsin B inhibitor, tokaramide A (1) has been isolated from the marine sponge Theonella aff. mirabilis. Its structure was determined by spectroscopic and chemical methods. Tokaramide A inhibits cathepsin B with an IC₅₀ value of 29.0 ng/mL.     

化学生态学在海洋污损生物防除中的应用

在海洋环境中,许多海洋生物都能产生对环境无危害的、具有防污活性的次生代谢产物以保护自身的洁净,利于自身的生存.用化学生态学的方法从海洋生物中提取天然防除物质成为近年来解决海洋污损生物问题的新思路,其目标是寻找高效无毒的防污材料取代原有的对海洋环境有严重危害的化学合成防污材料.虽然目前对提取生物的次生代谢产物的防污机理还所知甚少,但不少从海洋生物中获得的天然产物已显示出良好的防污活性.要解决污损生物防污问题,还需对天然产物的作用机制、生态学效应、天然产物与涂料的结合、控制和释放及野外实验进行更加深入的研究与探讨.     

含邻烷基肉桂酰结构单元天然产物的发现与生物合成研究进展

日益严峻的抗生素耐药性现象已经成为危害世界公共卫生安全的巨大隐患,寻找结构新颖、活性良好的抗生素是全球所面临的共同挑战。近年来,越来越多的含邻烷基肉桂酰结构单元天然产物被发现,并因其独特的结构以及广泛而显著的生物活性而受到关注。这些化合物大部分具有抗菌、抗肿瘤和抗结核等多种生物活性,是重要的药物先导物,具有广阔的研究前景。本文首先在结构和活性上对2024年及之前报道的该类化合物进行归类总结;然后就邻烷基肉桂酰结构单元相关生物合成分子机制研究进展进行了综述,包括碳骨架组装过程、苯环形成以及二聚化反应机制;最后对含邻烷基肉桂酰结构单元活性天然产物的靶向发现策略进行了描述,并对未来的发展方向进行了展望,以期为相关系统性研究工作的开展提供参考。     

Screening for antibacterial and antifungal activities in marine benthic invertebrates from northern Norway

Benthic marine invertebrates collected from sub-Arctic regions of northern Norway, were found to be a promising source of novel bioactive compounds against human and fish pathogenic bacteria and fungi. Lyophilized material from seven species of ascidians, six sponges and one soft alcyonid coral were extracted with 60% acidified acetonitrile (ACN). After separation into an ACN-rich phase (ACN-extract) and an aqueous phase, and subsequent solid-phase extraction of the aqueous phase, fractions differing in polarity were obtained and screened for antibacterial and antifungal activities, along with the more lipophilic ACN-extracts. Antimicrobial activity was determined against two Gram-negative, two Gram-positive bacteria, and two strains of fungi. Notably, all the invertebrate species in the study showed activity against all four strains of bacteria and the two strains of fungi. In general, the aqueous fractions displayed highest antimicrobial activity, and the most potent extracts were obtained from the colonial ascidian Synoicum pulmonaria which displayed activity against bacteria and fungi at a concentration of 0.02 mg/ml; the lowest concentration tested.     

Marine actinomycete diversity and natural product discovery

Microbial natural products remain an important resource for drug discovery yet the microorganisms inhabiting the worlds oceans have largely been overlooked in this regard. The recent discovery of novel secondary metabolites from taxonomically unique populations of marine actinomycetes suggests that these bacteria add an important new dimension to microbial natural product research. Continued efforts to characterize marine actinomycete diversity and how adaptations to the marine environment affect secondary metabolite production will create a better understanding of the potential utility of these bacteria as a source of useful products for biotechnology.     

Metagenomic approaches to exploit the biotechnological potential of the microbial consortia of marine sponges

Natural products isolated from sponges are an important source of new biologically active compounds. However, the development of these compounds into drugs has been held back by the difficulties in achieving a sustainable supply of these often-complex molecules for pre-clinical and clinical development. Increasing evidence implicates microbial symbionts as the source of many of these biologically active compounds, but the vast majority of the sponge microbial community remain uncultured. Metagenomics offers a biotechnological solution to this supply problem. Metagenomes of sponge microbial communities have been shown to contain genes and gene clusters typical for the biosynthesis of biologically active natural products. Heterologous expression approaches have also led to the isolation of secondary metabolism gene clusters from uncultured microbial symbionts of marine invertebrates and from soil metagenomic libraries. Combining a metagenomic approach with heterologous expression holds much promise for the sustainable exploitation of the chemical diversity present in the sponge microbial community.