Systematics-guided bioprospecting for bioactive microbial natural products

Advances in the taxonomic characterization of microorganisms have accelerated the rate at which new producers of natural products can be understood in relation to known organisms. Yet for many reasons, chemical efforts to characterize new compounds from new microbes have not kept pace with taxonomic advances. That there exists an ever-widening gap between the biological versus chemical characterization of new microorganisms creates tremendous opportunity for the discovery of novel natural products through the calculated selection and study of organisms from unique, untapped, ecological niches. A systematics-guided bioprospecting, including the construction of high quality libraries of marine microbes and their crude extracts, investigation of bioactive compounds, and increasing the active compounds by precision engineering, has become an efficient approach to drive drug leads discovery. This review outlines the recent advances in these issues and shares our experiences on anti-infectious drug discovery and improvement of avermectins production as well.     

Microbial structuring of marine ecosystems

Despite the impressive advances that have been made in assessing the diversity of marine microorganisms, the mechanisms that underlie the participation of microorganisms in marine food webs and biogeochemical cycles are poorly understood. Here, we stress the need to examine the biochemical interactions of microorganisms with ocean systems at the nanometre to millimetre scale--a scale that is relevant to microbial activities. The local impact of microorganisms on biogeochemical cycles must then be scaled up to make useful predictions of how marine ecosystems in the whole ocean might respond to global change. This approach to microbial oceanography is not only helpful, but is in fact indispensable.     

Tapping into microbial diversity

Even though significant advances have been made in understanding microbial diversity, most microorganisms are still only characterized by 'molecular fingerprints' and have resisted cultivation. Many different approaches have been developed to overcome the problems associated with cultivation of microorganisms because one obvious benefit would be the opportunity to investigate the previously inaccessible resources that these microorganisms potentially harbour.     

Biodiversity and potentials of marine-derived microorganisms

The marine environment is a prolific resource for the isolation of less exploited microorganisms. As a matter of fact, in the sea, untapped habitats exist with unique characteristics. In addition, the potential contribution of marine sources to the discovery of new bioactive molecules was recently recognized. Biosearch Italia possesses a collection of about 40 000 microorganisms, isolated from different ecological niches. In the search of new bioactive entities, investigations were expanded to marine habitats including marine sediments and organisms. More then 800 microorganisms have been isolated. About half belong to fungal genera, the others being actinomycetes. The frequency of antibiotic activities produced by these marine strains has been determined. Initial data are encouraging: marine isolates produce antibiotic activities with frequencies comparable to terrestrial ones. These activities probably represent a mixture of novel metabolites and known products previously discovered from terrestrial isolates. Further investigations are ongoing to assess the novelty of these observed microbiological activities.     

单细胞稳定同位素标记技术在固氮微生物中的应用研究

生物固氮是指固氮微生物将大气中氮气还原为生物可利用氨的过程,是环境中新氮的主要来源,调控初级生产力并影响氮储库的收支平衡。由于环境中大部分固氮微生物不可纯培养,不依赖培养且具有高空间分辨率水平的单细胞技术,成为研究固氮微生物的有力手段。~(15)N_2稳定同位素标记技术,以微生物对~(15)N的同化量或速率为依据,是表征微生物固氮活性的最直接手段。本文对~(15)N_2稳定同位素标记结合两种单细胞技术,即纳米二次离子质谱(Nano SIMS)和单细胞拉曼光谱,用于固氮微生物研究的最新进展进行了综述,内容包括揭示环境中高活性固氮微生物、空间分布、与其他生物的共生关系、细胞生理状态等,并进一步对近期发展的基于单细胞拉曼光谱的固氮微生物研究进行了展望。     

水圈微生物：推动地球重要元素循环的隐形巨人

正生活在水圈环境中的微生物数量巨大、遗传与代谢方式极为多样,它们驱动着地球上重要元素的循环。水圈微生物研究已经成为生命科学与地球科学的研究热点。国家自然科学基金委员会于2017年启动了"水圈微生物驱动地球元素循环的机制"重大研究计划(简称"水圈微生物"计划)。"水圈微生物"计划拟选择典型水圈生境,通过多学科交叉研究,借助新技术、新方法,揭示水圈微生物在物种、群落和生态水平驱动碳氮硫循环的机制及其环境响应,     

具有抑菌活性的海洋细菌的分离与鉴定

分离并筛选具有抑菌活性的海洋细菌对于开发和利用海洋微生物具有重要意义,该研究从6份海泥样品中共分离到78株海洋细菌,以6种细菌作为敏感指示菌,采用覆盖技术对分离菌株进行拮抗试验,17株海洋细菌具有抑菌活性,对其中2株具有较强抑菌活性的海洋细菌进行革兰氏染色,耐盐试验,运动性观察,过氧化氢酶测定,明胶液化试验,硫化氢产生试验,石蕊牛奶试验,糖类发酵,硝酸盐还原等特性分析,依据《伯杰氏细菌鉴定手册》进行分类鉴定,它们分别应归属为气单孢菌属（Aeromonas sp.）和假单孢菌属（Pseudomonas sp.）。     

海洋养殖环境微生物多样性及其作用

微生物是海洋养殖环境和海洋牧场生态系统中的关键环境因素之一，在牧场环境的物质循环、水质保障、饵料供应、水产健康等方面起重要作用，是营造海洋牧场环境且影响其可持续发展的重要因素。主要围绕海洋养殖环境中的病原微生物以及有益微生物两方面，概述了我国海洋养殖环境常见的病原性细菌、真菌、病毒以及相应的病害防治措施等，并介绍了海洋养殖环境中能够改善海水养殖环境，包括降低水体氨氮含量、降解水体硫化物、抑制赤潮藻类的生长等以及直接促进海水养殖生物生长的有益功能微生物类群。目前，我国关于海洋牧场环境营造过程中微生物的研究仍很少，而与海洋牧场环境有一定相似性的海水养殖环境中微生物的研究较为成熟，其对海洋牧场环境健康营造有很好的启示。海洋水产养殖环境中微生物的新功能菌种的发现、作用机制以及功能菌应用等方面的深入研究将会对我国大力推进海洋牧场建设起到重要的作用。     

Inhibition of the development of microorganisms (bacteria and fungi) by extracts of marine algae from Brittany, France

The inhibitory effects of aqueous, ethanolic and dichloromethane fractions from 16 marine algae from the Atlantic shores of North-East Brittany, France, have been investigated against microorganisms frequently associated with immersed surfaces. The extracts were tested in vitro against isolates of marine fungi, bacteria and yeasts potentially involved at different stages in the formation of biofilms in the sea. The high levels of inhibitory activity of nine extracts against marine fungi and Gram-positive bacteria and their apparent absence of toxicity against larvae of oysters and sea urchins suggests a potential for novel active ingredients. Received: 30 December 1998 / Received revision: 25 April 2000 / Accepted: 1 May 2000     

海洋固氮微生物与环境因子关系综述

海洋微生物的固氮作用是海洋氮素循环中一个关键的环节,对海洋生态系统的氮素供给和初级生产力的提高有着重要的意义。本文从海洋生物固氮的研究历史着手,详述了海洋固氮微生物的多样性及固氮活性研究方法,同时从环境因子的角度,总结了CO2浓度、季节变化、营养盐浓度、污染物及生物物种等环境因子对固氮微生物固氮活性的影响,并对海洋固氮微生物的研究前景进行了展望。     

A century of Chinook salmon consumption by marine mammal predators in the Northeast Pacific Ocean

As many marine mammal populations have increased following bans on their harvest, there has been a growing need to understand potential impacts of these population changes on coastal marine ecosystems. Quantifying consumption of prey species, such as fish, is particularly important when those same prey are also targeted by commercial fisheries. Estimating the impact of marine mammal predators on prey fish depends upon knowledge of marine mammal diet composition; scientific advances over the last century have improved understanding of diets but have also led to inconsistent methods that challenge attempts at synthesis and comparison. Meta-analysis techniques offer the opportunity to overcome such challenges, yet have not been widely applied to synthesize marine mammal diets over space and time. As a case study, we focus on synthesizing diet studies of Chinook (king) salmon (Oncorhynchus tshawytscha) by four species of marine mammal predators in the Northeast Pacific Ocean: Steller sea lions (Eumetopias jubatus), California sea lions (Zalophus californianus), harbor seals (Phoca vitulina), and killer whales (Orcinus orca). We also highlight several simple meta-analyses for which these types of diet databases may be employed. Our assembled database consists of > 330 records, spanning more than 100 years. Results indicate that the frequency of occurrence of Chinook salmon in killer whale studies is high (63%) relative to pinniped studies (< 10%). They also suggest a strong increasing ability to discriminate Chinook salmon from other salmonids, which we attribute to switches in diet studies from lethal or observational sampling toward molecular methods (DNA, fatty acids). Our database and analysis code are published as supplementary material, which we hope will be useful for other researchers and will inspire more of these syntheses.     

The Earth's bounty: assessing and accessing soil microbial diversity.

The study of microbial diversity represents a major opportunity for advances in biology and biotechnology. Recent progress in molecular microbial ecology shows that the extent of microbial diversity in nature is far greater than previously thought. Here, we discuss methods to analyse microorganisms from natural environments without culturing them and new approaches for gaining access to the genetic and chemical resources of these microorganisms.     

海洋动物来源微生物的共培养研究进展

近年来,由于一些新疾病的发生和细菌耐药性的出现,微生物来源次级代谢产物的筛选重复率越来越高,微生物一些代谢基因在现有实验室条件下无法表达,所以需要发现新的微生物资源,同时找到激活微生物代谢产物基因的方法.海洋动物体内蕴含着大量的共附生微生物资源,可以产生很多具有生物活性的化合物,是潜在的药用资源.本文综述了近年来海洋动...     

海洋动物来源微生物分离培养的新方法

海洋动物体内有着丰富的微生物,它们可以帮助动物宿主合成一些营养物质或者抵御其他动物侵害所需的化合物。在海洋动物来源微生物的生物活性化合物中,目前已有功能较好且应用于临床治疗的化合物。由于实验室分离培养条件的限制,目前仅有小部分的微生物被分离利用。因此开展新颖而有效的海洋动物来源微生物分离培养方法的研究十分必要。本文概括了近些年从海洋动物中分离微生物的新方法的结果和不足,这些方法包括原位培养技术、电回收法和培养基的改良等,重点介绍了扩散盒技术、I-tip技术和微囊包埋技术等。这些新方法的应用有助于获得更多新的微生物菌种和微生物次生代谢产物,了解微生物与动物宿主之间的关系,以及扩大海洋微生物资源的开发和利用。     

“海洋生态系统工程师”及其生态作用

“海洋生态系统工程师”是能够塑造栖息地并使其他海洋生物受益的海洋生物种类。海洋中的植物、动物和微生物中均存在为其他生物种类塑造栖息地的“海洋生态系统工程师”,它们的生态作用是其发挥生态功能的基础。本文基于国内外相关文献,系统阐述了“海洋生态系统工程师”生态作用的相关研究进展,并对今后的主要研究方向和内容提出建议。“海洋生态系统工程师”能够在特定的海洋环境中发挥积极作用,但一旦成为入侵种可能会对入侵海域产生负面影响;有些“海洋生态系统工程师”在发挥积极作用的同时也会在不同程度上带来负面影响。今后,应加强海洋生物床、海洋生物礁、海洋生物膜和复合生态系统工程等研究,有效利用“海洋生态系统工程师”的积极作用并防控其负面影响,实现对海洋的综合开发利用和保护。     

Biologically active metabolites of the marine actinobacteria

This review systematically data on the chemical structure and biological activity of metabolites of obligate and facultative marine actinobacteria, published from 2000 to 2007. We discuss some structural features of the five groups of metabolites related to macrolides and compounds containing lactone, quinone and diketopiperazine residues, cyclic peptides, alkaloids, and compounds of mixed biosynthesis. Survey shows a large chemical diversity of metabolites actinobacteria isolated from marine environment. It is shown that, along with metabolites, identical to previously isolated from terrestrial actinobacteria, marine actinobacteria synthesize unknown compounds not found in other natural sources, including micro organisms. Perhaps the biosynthesis of new chemotypes bioactive compounds in marine actinobacteria is one manifestation of chemical adaptation of microorganisms to environmental conditions at sea. Review stresses the importance of the chemical study of metabolites of marine actinobacteria. These studies are aimed at obtaining new data on marine microorganisms producers of biologically active compounds and chemical structure and biological activity of new low-molecular bioregulators of natural origin.     

Marine microorganisms as a source of bioactive agents

Several ecological factors of the marine environment were used in developing a strategy for discovering useful bioactive agents from marine microorganisms. By consideration of sea water requirements, production and degradation of marine polymers, and plasmid content, several novel anti-malarial antibiotics, anti-tumor polysaccharides, glucan-degrading enzymes, and aminoglycoside antibiotics were found.     

When Pasteurian Science Went to Sea: The Birth of Marine Microbiology

In the late nineteenth century, French naturalists were global leaders in microbial research. Louis Pasteur advanced sterilization techniques and demonstrated that dust particles in the air could contaminate a putrefiable liquid. Pasteur’s discoveries prompted a new research program for the naturalists of the Talisman and Travailleur expeditions: to recover uncontaminated water and mud samples from the deep sea. French naturalists Adrien Certes and Paul Regnard both independently conducted experiments to address the question of whether microorganisms inhabited the oceans and whether organic material in the deep sea was subject to decomposition. The experiments of Certes and Regnard have largely been omitted from histories of microbiology and marine science. However, an examination of their work is crucial for understanding the context in which marine microbiology first developed. At the end of the nineteenth century, marine microbiology emerged from the disciplinary melding of terrestrial microbial ecology, experimental physiology, and the then-nascent field of deep-sea biology.     

Lessons from sea louse and salmon epidemiology

Effective disease management can benefit from mathematical models that identify drivers of epidemiological change and guide decision-making. This is well illustrated in the host–parasite system of sea lice and salmon, which has been modelled extensively due to the economic costs associated with sea louse infections on salmon farms and the conservation concerns associated with sea louse infections on wild salmon. Consequently, a rich modelling literature devoted to sea louse and salmon epidemiology has been developed. We provide a synthesis of the mathematical and statistical models that have been used to study the epidemiology of sea lice and salmon. These studies span both conceptual and tactical models to quantify the effects of infections on host populations and communities, describe and predict patterns of transmission and dispersal, and guide evidence-based management of wild and farmed salmon. As aquaculture production continues to increase, advances made in modelling sea louse and salmon epidemiology should inform the sustainable management of marine resources.     

Biotechnology and bioremediation: successes and limitations

With advances in biotechnology, bioremediation has become one of the most rapidly developing fields of environmental restoration, utilizing microorganisms to reduce the concentration and toxicity of various chemical pollutants, such as petroleum hydrocarbons, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, phthalate esters, nitroaromatic compounds, industrial solvents, pesticides and metals. A number of bioremediation strategies have been developed to treat contaminated wastes and sites. Selecting the most appropriate strategy to treat a specific site can be guided by considering three basic principles: the amenability of the pollutant to biological transformation to less toxic products (biochemistry), the accessibility of the contaminant to microorganisms (bioavailability) and the opportunity for optimization of biological activity (bioactivity). Recent advances in the molecular genetics of biodegradation and studies on enzyme-tailoring and DNA-shuffling are discussed in this paper.