Isolation strategies of marine-derived actinomycetes from sponge and sediment samples

During the last two decades, discoveries of new members of actinomycetes and novel metabolites from marine environments have drawn attention to such environments, such as sediment and sponge. For the successful isolation of actinomycetes from marine environments, many factors including the use of enrichment and pre-treatment techniques, and the selection of growth media and antibiotic supplements should be taken into account. High-throughput cultivation is an innovative technique that mimics nature, eliminates undesired, fast-growing bacteria and creates suitable conditions for rare, slow-growing actinomycetes. This review comprehensively evaluates the traditional and innovative techniques and strategies used for the isolation of actinomycetes from marine sponge and sediment samples.     

Systematic and biotechnological aspects of halophilic and halotolerant actinomycetes

More than 70 species of halotolerant and halophilic actinomycetes belonging to at least 24 genera have been validly described. Halophilic actinomycetes are a less explored source of actinomycetes for discovery of novel bioactive secondary metabolites. Degradation of aliphatic and aromatic organic compounds, detoxification of pollutants, production of new enzymes and other metabolites such as antibiotics, compatible solutes and polymers are other potential industrial applications of halophilic and halotolerant actinomycetes. Especially new bioactive secondary metabolites that are derived from only a small fraction of the investigated halophilic actinomycetes, mainly from marine habitats, have revealed the huge capacity of this physiological group in production of new bioactive chemical entities. Combined high metabolic capacities of actinomycetes and unique features related to extremophilic nature of the halophilic actinomycetes have conferred on them an influential role for future biotechnological applications.     

Marine actinomycetes as an emerging resource for the drug development pipelines

Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinomycetes from terrestrial sources have been studied and screened since the 1950s, yielding many important anti-infective and anti-cancer drugs. However, frequent re-discovery of the same compounds in terrestrial actinomycetes have made them less attractive for screening programs in the recent years. At the same time, actinomycetes isolated from the marine environment currently receive considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. This review highlights achievements and challenges in the isolation of marine actinomycetes, some examples of bioactive metabolites identified by conventional screening, and presents new developments in the field of genome mining and heterologous expression of biosynthetic gene clusters leading to the discovery of novel compounds.     

Bioactive compounds from marine actinomycetes

Actinomycetes are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Among its various genera, Streptomyces, Saccharopolyspora, Amycolatopsis, Micromonospora and Actinoplanes are the major producers of commercially important biomolecules. Several species have been isolated and screened from the soil in the past decades. Consequently the chance of isolating a novel actinomycete strain from a terrestrial habitat, which would produce new biologically active metabolites, has reduced. The most relevant reason for discovering novel secondary metabolites is to circumvent the problem of resistant pathogens, which are no longer susceptible to the currently used drugs. Existence of actinomycetes has been reported in the hitherto untapped marine ecosystem. Marine actinomycetes are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, insecticidal and enzyme inhibition. Bioactive compounds from marine actinomycetes possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens.     

专性海洋放线菌盐孢菌的研究进展

盐孢菌属(Salinispora)作为首个被报道的专性海洋放线菌,主要分布于热带和亚热带海洋沉积环境中,在海绵、海鞘中也有发现。与其他大多数放线菌一样,盐孢菌属的菌株可以产生大量具有抗细菌、抗病毒、抗肿瘤细胞活性、结构新颖的次级代谢产物且表现出物种特异性。全基因组序列分析显示,盐孢菌属菌株基因组中超过10%的基因序列与次级代谢产物合成相关,但绝大多数生物合成基因簇编码的产物未被发现,表明盐孢菌属还存在巨大的生物合成潜能,有待深入发掘。目前新的培养方法、测序技术及生物信息学、基因组发掘技术、合成生物学技术的发展对提升盐孢菌属菌株新型药物的生产潜力发挥重要作用。本文对盐孢菌属的物种多样性、系统分类与化合物发现等方面的研究进行了系统综述。     

Unique Actinomycetes from Marine Caves and Coral Reef Sediments Provide Novel PKS and NRPS Biosynthetic Gene Clusters

In the ever-expanding search for novel bioactive molecules and enzymes, marine actinomycetes have proven to be a productive source. While open reef sediment and sponge-associated actinomycetes have been extensively examined, their marine cave counterparts remain unevaluated. Anchialine cave systems in the Bahamas offered an ideal setting to evaluate the occurrence and variation within sediment-associated actinomycete communities. While in close geographical proximity to open reef environments, these systems provide a specialized environmental niche devoid of light and direct exposure to nutrient input. In the present study, selective isolation techniques and molecular methods were used to test the hypothesis that variable distribution of actinomycetes and secondary metabolite gene clusters occur between open reef and marine cave systems. The results indicated that differences exist within the culturable sediment-associated actinomycete communities between marine caves and open reef systems, with members of the genus Streptomyces dominating cultures from open reef sediments and a more diverse suite of actinomycetes isolated from marine cave sediment samples. Within the cave isolates, members of the proposed genus Solwaraspora were the most represented. Based on PKS- and NRPS-gene-targeted PCR amplification and sequencing, geographic variation in the occurrence of these biosynthetic pathways was also observed. These findings indicate that marine cave systems are a lucrative source in the search for novel secondary metabolite producers with biotechnological applications and that environmental and geographic factors likely affect the occurrence of these biosynthetic pathways.     

Hybrid isoprenoid secondary metabolite production in terrestrial and marine actinomycetes

Terpenoids are among the most ubiquitous and diverse secondary metabolites observed in nature. Although actinomycete bacteria are one of the primary sources of microbially derived secondary metabolites, they rarely produce compounds in this biosynthetic class. The terpenoid secondary metabolites that have been discovered from actinomycetes are often in the form of biosynthetic hybrids called hybrid isoprenoids (HIs). HIs include significant structural diversity and biological activity and thus are important targets for natural product discovery. Recent screening of marine actinomycetes has led to the discovery of a new lineage that is enriched in the production of biologically active HI secondary metabolites. These strains represent a promising resource for natural product discovery and provide unique opportunities to study the evolutionary history and ecological functions of an unusual group of secondary metabolites.     

Marine actinomycetes: An ongoing source of novel bioactive metabolites

Actinomycetes are virtually unlimited sources of novel compounds with many therapeutic applications and hold a prominent position due to their diversity and proven ability to produce novel bioactive compounds. There are more than 22,000 known microbial secondary metabolites, 70% of which are produced by actinomycetes, 20% from fungi, 7% from Bacillus spp. and 1–2% by other bacteria. Among the actinomycetes, streptomycetes group are considered economically important because out of the approximately more than 10,000 known antibiotics, 50–55% are produced by this genus. The ecological role of actinomycetes in the marine ecosystem is largely neglected and various assumptions meant there was little incentive to isolate marine strains for search and discovery of new drugs. The search for and discovery of rare and new actinomycetes is of significant interest to drug discovery due to a growing need for the development of new and potent therapeutic agents. Modern molecular technologies are adding strength to the target-directed search for detection and isolation of bioactive actinomycetes, and continued development of improved cultivation methods and molecular technologies for accessing the marine environment promises to provide access to this significant new source of chemical diversity with novel/rare actinomycetes including new species of previously reported actinomycetes.     

Marine actinomycetes as a source of novel secondary metabolites

A set of 600 actinomycetes strains which were isolated from marine sediments from various sites in the Pacific and Atlantic Oceans were screened for the production of bioactive secondary metabolites. Marine streptomycete strains were found to be producers of well known chemically diverse antibiotics isolated from terrestrial streptomycetes, as in the case of marine Micromonospora strains. New marine members of the rare genus Verrucosispora seem to be a promising source for novel bioactive secondary metabolites as shown in the case of the abyssomicin producing strain AB-18-032.     

海洋放线菌的研究现状及未来展望

【背景】放线菌具有丰富的遗传和功能多样性,其次级代谢产物活性广泛,在临床医疗、农业生产和污染防治等领域都发挥着重要的作用。海洋放线菌由于其特殊的代谢途径,能产生独特的活性天然产物而受到广泛关注。【目的】探究国内外海洋放线菌领域研究的热点和趋势,为后续研究提供参考。【方法】以“marine actinomycetes or marine actinobacteria”为关键词,在Web of Science中检索海洋放线菌领域的文章进行计量分析,使用VOSviewer软件对其关键词、国家、机构、作者、发表时间进行可视化分析。【结果】海洋放线菌领域的文章发表数量总体呈逐年上升趋势,主要集中在微生物学及药学领域,中美两国在论文数量和引用频次上远超其他国家,海洋放线菌领域的研究集中在菌株的分离鉴定、活性天然产物挖掘以及生物信息学等方面。【结论】海洋放线菌在全球范围内愈发受到重视,国内外机构应当加强合作,运用生物信息学技术进一步挖掘活性次级代谢产物,推动海洋放线菌领域进一步发展。     

Phylogenetic characterization of culturable actinomycetes associated with the mucus of the coral Acropora digitifera from Gulf of Mannar

The marine environment is a virtually untapped source of novel actinomycete diversity and its metabolites. Investigating the diversity of actinomycetes in other marine macroorganisms, like seaweeds and sponges, have resulted in isolation of novel bioactive metabolites. Actinomycetes diversity associated with corals and their produced metabolites have not yet been explored. Hence, in this study we attempted to characterize the culturable actinomycetes population associated with the coral Acropora digitifera. Actinomycetes were isolated from the mucus of the coral wherein the actinomycetes count was much higher when compared with the surrounding seawater and sediment. Actinobacteria-specific 16S rRNA gene primers were used for identifying the isolates at the molecular level in addition to biochemical tests. Amplified ribosomal DNA restriction analysis using three restriction enzymes revealed several polymorphic groups within the isolates. Sequencing and blast analysis of the isolates revealed that some isolates had only 96.7% similarity with its nearest match in GenBank indicating that they may be novel isolates at the species level. The isolated actinomycetes exhibited good antibacterial activity against various human pathogens. This study offers for the first time a prelude about the unexplored culturable actinomycetes diversity associated with a scleractinian coral and their bioactive capabilities.     

海洋放线菌Marinactinospora thermotolerans的研究进展

海洋放线菌以产生多种活性天然产物而著称,其中部分结构新颖的活性化合物具有发展成为新药的巨大潜力,引起国内外相关领域研究人员的极大关注。同时,也促进了我国海洋放线菌研究工作的全面展开。本文系统综述了海洋放线菌新属种Marinactinospora thermotolerans的分类鉴定、新颖的次级代谢产物的发现及其生物合成机制以及该菌株的全基因组生物信息学分析等方面的最新研究进展,以期能为其他海洋放线菌新属种的分类鉴定、活性次级代谢产物的发现和生物合成机制研究提供借鉴作用。     

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.     

Natural products potential of Dictyoceratida sponges-associated micro-organisms

The marine environment represents one of the most underexplored environments in the world. Marine sponges have a higher taxonomic diversity according to definite environmental conditions. They have been considered interesting sources for bioactive compounds. Dictyoceratida sponges are divided into five families which are widely distributed and habituating different types of micro-organisms. However, some secondary metabolites are probably not produced by the sponges themselves, but rather by their associated micro-organisms. These secondary metabolites are characterized by different chemical structures and consequently different biological activities. This review outlines the reported secondary metabolites from micro-organisms associated with Dictyoceratida sponges and their investigated biological activities from 1991 to 2019. The increasing research studies in this field can play a major role in marine microbial natural products drug discovery in the future.     

可培养海洋放线菌生物多样性的研究进展

海洋放线菌是新药开发和天然活性产物的重要来源,海洋放线菌的生物多样性是代谢产物功能多样性的基础,因此研究可培养放线菌的生物多样性具有重要的意义。综述了近年来可培养的海洋放线菌生物多样性的研究进展,尤其是海绵共附生放线菌、深海放线菌和海洋固有放线菌的研究进展,对可培养的海洋放线菌的分离培养方法,包括样品处理、培养基的选择等进行了重点介绍,并对未培养海洋放线菌的分离培养进行了探讨,强调了建立区域性海洋放线菌菌种及基因资源库的重要性。     

植物内生放线菌多样性研究进展

植物内生放线菌作为植物内生菌资源的一大类,具有丰富的多样性,其次级代谢产物也十分丰富,而且还具有各种生物学活性。通过了解植物内生放线菌资源的多样性,可以对其产生的生物活性物质进行筛选和分析,从而筛选出具有良好药理活性的物质应用于临床。从植物内生放线菌宿主植物、组织分布、种类和数量以及活性基因4个方面综述了植物内生放线菌的多样性资源,介绍植物内生放线菌新的微生物物种,总结了植物内生放线菌目前研究中存在的问题及展望。     

A guide to successful bioprospecting: informed by actinobacterial systematics

New structurally diverse natural products are discovered when novel screening procedures are introduced or when high quality biological materials from new sources are examined in existing screens, hence it is important to foster these two aspects of novelty in drug discovery programmes. Amongst prokaryotes, actinomycetes, notably streptomycetes, remain a rich source of new natural products though it has become increasingly difficult to find such metabolites from common actinomycetes as screening ‘old friends’ leads to the costly rediscovery of known compounds. The bioprospecting strategy which is the subject of this review is based upon the premise that new secondary metabolites can be found by screening relatively small numbers of dereplicated, novel actinomycetes isolated from marine sediments. The success of the strategy is exemplified by the discovery of a range of novel bioactive compounds, notably atrop-abyssomicin C and proximicins A, B and C from Verrucosispora strains isolated from sediment samples taken from the Sea of Japan and the Raune Fjord, respectively, and the dermacozines derived from Dermacoccus strains isolated from the Challenger Deep of the Mariana Trench in the Pacific Ocean. The importance of current advances in prokaryotic systematics in work of this nature is stressed and a plea made that resources be sought to train, support and employ the next generation of actinobacterial systematists.     

Saccharopolyspora: an underexplored source for bioactive natural products

Actinomycetes are a rich source for secondary metabolites with a diverse array of biological activities. Among the various genera of actinomycetes, the genus Saccharopolyspora has long been recognized as a potential source for antibiotics and other therapeutic leads that belong to diverse classes of natural products. Members of the genus Saccharopolyspora have been widely reported from several natural sources including both terrestrial and marine environments. A plethora of this genus has been chemically investigated for the production of novel natural products with interesting pharmacological effects. Therefore, Saccharopolyspora is considered one of the pharmaceutical important genera that could provide further chemical diversity with potential lead compounds. In this review, the literature from 1976 until December 2018 was covered, providing a comprehensive survey of all natural products derived from this genus and their semi-synthetic derivatives along with their biological activities, whenever applicable. Moreover, the biological diversity of Saccharopolyspora species and their habitats were also discussed.     

放线菌药物资源开发面临的问题与对策

放线菌药物的开发已取得了极其辉煌的成就, 对医疗事业的发展和人类健康做出了重大贡献。然而, 随着放线菌药物资源的长期开发和利用, 也面临诸多问题。如: 包袱沉重, 去重复难度极大, 因而投资周期长、耗资巨, 风险大; 药物开发赶不上病原菌抗药性的增加及不断出现的新疾病; 虽然未知放线菌甚多, 但发现难度大。为此, 提出了从化学、菌种和基因三方面开展放线菌药物研究的应对策略, 以解决限制放线菌药物资源持续利用和发展的瓶颈。     

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.