Special Issue "Bioactive Compounds from Marine Microbes"
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A special issue of Marine Drugs (ISSN 1660-3397).
Deadline for manuscript submissions: closed (31 July 2011)
Special Issue Editor
Guest Editor
Dr. Kirk R. Gustafson
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Building 562, Room 201, Frederick, MD 21702-1201, USA
Website: http://ccr.cancer.gov/staff/staff.asp?profileid=7125
E-Mail: gustafki@mail.nih.gov
Phone: +1 301 846 5197
Fax: +1 301 846 6157
Interests: natural products chemistry; chemical biology of natural products; NMR spectroscopy
Special Issue Information
Dear Colleagues,
The marine environment is a vast and largely unexplored resource for accessing diverse communities of microorganisms with novel biosynthetic capabilities. Marine habitats provide unique conditions for microbial growth and secondary metabolite expression that are not found in terrestrial ecosystems. The co-evolution of many marine macroorganisms, particularly invertebrate animals, with these microbes has often lead to the development of very close associations or symbiotic relationships between the host organism and a specific microbe. This in turn has resulted in the development and elaboration of unique microbial biosynthetic pathways and capabilities that can be utilized to generate novel compounds. Marine sediments are also now recognized as a rich source of microbial taxonomic diversity and new biologically active compounds. Efforts to cultivate and evaluate marine microorganisms and the associated compounds they can produce have expanded significantly in recent years, but this are of study is still very much in its infancy considering the vastness of the marine environment and the different types of microbial habitats found there.
Kirk R. Gustafson Ph. D.
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).
Keywords
- actinomycetes
- bacteria
- biosynthesis
- dereplication
- fungi
- metabolic modulators and elicitors
- micro algae
- quorum sensing
- symbionts
Published Papers (10 papers)
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Received: 18 September 2009; in revised form: 28 October 2009 / Accepted: 29 October 2009 / Published: 2 November 2009
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Abstract: Members of the marine dinoflagellate genus Alexandrium are known to exude allelochemicals, unrelated to well-known neurotoxins (PSP-toxins, spirolides), with negative effects on other phytoplankton and marine grazers. Physico/chemical characterization of extracellular lytic compounds of A. tamarense, quantified by Rhodomonas salina bioassay, showed that the lytic activity, and hence presumably the compounds were stable over wide ranges of temperatures and pH and were refractory to bacterial degradation. Two distinct lytic fractions were collected by reversed-phase solid-phase extraction. The more hydrophilic fraction accounted for about 2% of the whole lytic activity of the A. tamarense culture supernatant, while the less hydrophilic one accounted for about 98% of activity. Although temporal stability of the compounds is high, substantial losses were evident during purification. Lytic activity was best removed from aqueous phase with chloroform-methanol (3:1). A “pseudo-loss” of lytic activity in undisturbed and low-concentrated samples and high activity of an emulsion between aqueous and n-hexane phase after liquid-liquid partition are strong evidence for the presence of amphipathic compounds. Lytic activity in the early fraction of gel permeation chromatography and lack of activity after 5 kD ultrafiltration indicate that the lytic agents form large aggregates or macromolecular complexes.

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Received: 12 October 2009; in revised form: 18 November 2009 / Accepted: 19 November 2009 / Published: 23 November 2009
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Abstract: We isolated a pol inhibitor from the cultured mycelia extract of a fungal strain isolated from natural salt from a sea salt pan in Australia, which was identified as 3-O-methylfunicone by spectroscopic analyses. This compound selectively inhibited the activities of mammalian Y-family DNA polymerases (pols) (i.e., pols η, ι and κ). Among these pols, human pol κ activity was most strongly inhibited, with an IC50 value of 12.5 μM. On the other hand, the compound barely influenced the activities of the other families of mammalian pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and showed no effect on the activities of fish pol δ, plant pols, prokaryotic pols and other DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I. This compound also suppressed the growth of two cultured human cancer cell lines, HCT116 (colon carcinoma cells) and HeLa (cervix carcinoma cells), and UV-treated HeLa cells exhibited lower clonogenic survival in the presence of inhibitor.

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Received: 18 January 2010; in revised form: 3 February 2010 / Accepted: 22 February 2010 / Published: 1 March 2010
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Abstract: While the oceans cover more than 70% of the Earth’s surface, marine derived microbial natural products have been largely unexplored. The marine environment is a habitat for many unique microorganisms, which produce biologically active compounds (“bioactives”) to adapt to particular environmental conditions. For example, marine surface associated microorganisms have proven to be a rich source for novel bioactives because of the necessity to evolve allelochemicals capable of protecting the producer from the fierce competition that exists between microorganisms on the surfaces of marine eukaryotes. Chemically driven interactions are also important for the establishment of cross-relationships between microbes and their eukaryotic hosts, in which organisms producing antimicrobial compounds (“antimicrobials”), may protect the host surface against over colonisation in return for a nutrient rich environment. As is the case for bioactive discovery in general, progress in the detection and characterization of marine microbial bioactives has been limited by a number of obstacles, such as unsuitable culture conditions, laborious purification processes, and a lack of de-replication. However many of these limitations are now being overcome due to improved microbial cultivation techniques, microbial (meta-) genomic analysis and novel sensitive analytical tools for structural elucidation. Here we discuss how these technical advances, together with a better understanding of microbial and chemical ecology, will inevitably translate into an increase in the discovery and development of novel drugs from marine microbial sources in the future.
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Received: 28 January 2010; in revised form: 26 February 2010 / Accepted: 16 March 2010 / Published: 17 March 2010
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Abstract: Bacteria in marine environments are often under extreme conditions of e.g., pressure, temperature, salinity, and depletion of micronutrients, with survival and proliferation often depending on the ability to produce biologically active compounds. Some marine bacteria produce biosurfactants, which help to transport hydrophobic low water soluble substrates by increasing their bioavailability. However, other functions related to heavy metal binding, quorum sensing and biofilm formation have been described. In the case of metal ions, bacteria developed a strategy involving the release of binding agents to increase their bioavailability. In the particular case of the Fe3+ ion, which is almost insoluble in water, bacteria secrete siderophores that form soluble complexes with the ion, allowing the cells to uptake the iron required for cell functioning. Adaptive changes in the lipid composition of marine bacteria have been observed in response to environmental variations in pressure, temperature and salinity. Some fatty acids, including docosahexaenoic and eicosapentaenoic acids, have only been reported in prokaryotes in deep-sea bacteria. Cell membrane permeability can also be adapted to extreme environmental conditions by the production of hopanoids, which are pentacyclic triterpenoids that have a function similar to cholesterol in eukaryotes. Bacteria can also produce molecules that prevent the attachment, growth and/or survival of challenging organisms in competitive environments. The production of these compounds is particularly important in surface attached strains and in those in biofilms. The wide array of compounds produced by marine bacteria as an adaptive response to demanding conditions makes them suitable candidates for screening of compounds with commercially interesting biological functions. Biosurfactants produced by marine bacteria may be helpful to increase mass transfer in different industrial processes and in the bioremediation of hydrocarbon-contaminated sites. Siderophores are necessary e.g., in the treatment of diseases with metal ion imbalance, while antifouling compounds could be used to treat man-made surfaces that are used in marine environments. New classes of antibiotics could efficiently combat bacteria resistant to the existing antibiotics. The present work aims to provide a comprehensive review of the metabolites produced by marine bacteria in order to cope with intrusive environments, and to illustrate how such metabolites can be advantageously used in several relevant areas, from bioremediation to health and pharmaceutical sectors.
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Received: 6 February 2010; in revised form: 28 March 2010 / Accepted: 1 April 2010 / Published: 4 April 2010
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Abstract: As the association of marine animals with bacteria has become more commonly recognized, researchers have increasingly questioned whether these animals actually produce many of the bioactive compounds originally isolated from them. Bacteriocins, ribosomally synthesized antibiotic peptides, constitute one of the most potent weapons to fight against pathogen infections. Indeed, bacteriocinogenic bacteria may prevent pathogen dissemination by occupying the same ecological niche. Bacteriocinogenic strains associated with marine animals are a relevant source for isolation of probiotics. This review draws up an inventory of the marine bacteriocinogenic strains isolated from animal-associated microbial communities, known to date. Bacteriocin-like inhibitory substances (BLIS) and fully-characterized bacteriocins are described. Finally, their applications as probiotics in aquaculture are discussed.
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Received: 28 March 2011; in revised form: 20 April 2011 / Accepted: 4 May 2011 / Published: 12 May 2011
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Abstract: Three new bianthraquinone derivatives, alterporriol K (1), L (2) and M (3), along with six known compounds were obtained from extracts of the endophytic fungus Alternaria sp. ZJ9-6B, isolated from the mangrove Aegiceras corniculatum collected in the South China Sea. Their structures were elucidated by one- and two-dimensional NMR spectroscopy, MS data analysis and circular dichroism measurements. Compounds 1, 2 and 3 were first isolated alterporriols with a C-2–C-2′ linkage. The crystallographic data of tetrahydroaltersolanol B (7) was reported for the first time. In the primary bioassays, alterporriol K and L exhibited moderate cytotoxic activity towards MDA-MB-435 and MCF-7 cells with IC50 values ranging from 13.1 to 29.1 µM.
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Received: 25 June 2011; in revised form: 26 July 2011 / Accepted: 4 August 2011 / Published: 10 August 2011
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Abstract: The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders.
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Received: 10 July 2011; in revised form: 1 August 2011 / Accepted: 10 August 2011 / Published: 12 August 2011
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Abstract: Surface-associated marine bacteria often produce secondary metabolites with antagonistic activities. In this study, tropodithietic acid (TDA) was identified to be responsible for the antibacterial activity of the marine epiphytic bacterium Pseudovibrio sp. D323 and related strains. Phenol was also produced by these bacteria but was not directly related to the antibacterial activity. TDA was shown to effectively inhibit a range of marine bacteria from various phylogenetic groups. However TDA-producers themselves were resistant and are likely to possess resistance mechanism preventing autoinhibition. We propose that TDA in isolate D323 and related eukaryote-associated bacteria plays a role in defending the host organism against unwanted microbial colonisation and, possibly, bacterial pathogens.
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Received: 28 July 2011; in revised form: 11 August 2011 / Accepted: 15 August 2011 / Published: 25 August 2011
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Abstract: Bacteria belonging to the Vibrionaceae family are widespread in the marine environment. Today, 128 species of vibrios are known. Several of them are infamous for their pathogenicity or symbiotic relationships. Despite their ability to interact with eukaryotes, the vibrios are greatly underexplored for their ability to produce bioactive secondary metabolites and studies have been limited to only a few species. Most of the compounds isolated from vibrios so far are non-ribosomal peptides or hybrids thereof, with examples of N-containing compounds produced independent of nonribosomal peptide synthetases (NRPS). Though covering a limited chemical space, vibrios produce compounds with attractive biological activities, including antibacterial, anticancer, and antivirulence activities. This review highlights some of the most interesting structures from this group of bacteria. Many compounds found in vibrios have also been isolated from other distantly related bacteria. This cosmopolitan occurrence of metabolites indicates a high incidence of horizontal gene transfer, which raises interesting questions concerning the ecological function of some of these molecules. This account underlines the pending potential for exploring new bacterial sources of bioactive compounds and the challenges related to their investigation.

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Received: 19 July 2011; in revised form: 13 August 2011 / Accepted: 23 August 2011 / Published: 24 October 2011
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Abstract: It is known that some strains of Vibrio parahaemolyticus are responsible for gastroenteric diseases caused by the ingestion of marine organisms contaminated with these bacterial strains. Organic products that show inhibitory activity on the growth of the pathogenic V. parahaemolyticus were extracted from a Vibrio native in the north of Chile. The inhibitory organic products were isolated by reverse phase chromatography and permeation by Sephadex LH20, and were characterized by spectroscopic and spectrometric techniques. The results showed that the prevailing active product is oleic acid, which was compared with standards by gas chromatography and high-performance liquid chromatography (HPLC). These active products might be useful for controlling the proliferation of pathogenic clones of V. parahaemolyticus.
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Last update: 10 October 2012