Special Issue "Marine Dinoflagellates"

Guest Editor
Dr. Andrea Bourdelais
Center for Marine Science, University of North Carolina at Wilmington, 5600 Marvin K. Moss Lane, Wilmington NC, 28409, USA
E-Mail:
Interests: isolation and structure elucidation of bioactive marine natural products; polyether compounds; bioassay screening; high content screening; quantitative analysis of marine toxins; harmful algal blooms; Florida red tide; marine dinoflagellates

Dear Colleagues,

Dinoflagellates comprise a diverse class of flagellated protists found in marine and fresh water environments. Of the approximately 2000 living species about 1700 species are found in marine environments. Due to the complex nature of the marine environment these microorganisms have developed unique biosynthetic machinery for the production of metabolites with unusual chemical structures and potent biological activities. Naturally produced chemical families include polyethers, macrolides, polyhydroxy compounds, heterocycles, polyketals, amino acids, terpenes, phytopigments, and purine derivatives. Although metabolites produced by these micro-organisms are known for their cytotoxicity, many have show selective activity in biological systems for example: saxitoxins are selective sodium channel blockers, brevetoxins and ciguatoxins selectively activate sodium channels, and maitotoxins act on calcium channels. Other metabolites have been found to inhibit enzymes (okadaic acid), yet others have show potent activity as anti-fungal (gamberic acids) or anti-tumor (amphidinols) agents. Because of their unprecedented biosynthetic capabilities and ease of culture, dinoflagellates provide a renewable source for novel chemical structures that may be used as biological tools or drug candidates. This special issue will be devoted to the bioactivity of both natural and chemically modified dinoflagellate metabolites as well the biosynthetic pathways involved in their production.

Dr. Andrea J. Bourdelais
Guest Editor

Submission

All papers should be submitted to marinedrugs@mdpi.org with a copy to the Guest Editor. Papers will be published continuously until the deadline and will be listed together at the special issue website. Research articles and review articles are both invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editors for announcement on this website.

Submitted papers should not have been published previously, nor be under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors, sample copies and other relevant information for submitting papers are available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed quarterly journal published by Molecular Diversity Preservation International.

Please visit the Instructions for Authors page before submitting a paper. Open Access Article Processing Charges are 1000 CHF per paper. English correction fees (250 CHF) will be added in certain cases (1250 CHF per paper for those papers that require extensive additional formatting and/or English corrections.). Starting 1 January 2010, Article Processing Charges are of 1400 CHF per accepted article for Marine Drugs

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• marine natural products
• bioactive metabolites
• microalgae
• mechanism of action
• therapeutic potential
• polyethers
• phytopigments
• lipids
• marine toxins
• bioassays
• culturing
• bioactive compounds
• symbiotic relationships
• natural defenses
• biosynthesis
• semisynthetic derivatives
• bioactivity
• structure activity relationships
• environmental impact

Type of Paper: Review
Title: The Spirolide Family of Shellfish Toxins: Isolation, Structure, Biological Activity and Synthesis
Authors: Stéphanie M. Guéret and Margaret A. Brimble
Affiliation: The University of Auckland, 23 Symond Street, Auckland City, New Zealand; E-Mails: s.gueret@auckland.ac.nz, m.brimble@auckland.ac.nz
Abstract: Spirolides are metabolites of the dinoflagellate Alexandrium ostenfeldii. Spirolides (A-D) were isolated from the digestive glands of contaminated mussels (Mytilus edulis), scallops (Placopecten magellanicus) and toxic plankton from the East coast of Nova Scotia in Canada. 13 members of the spirolide family of marine biotoxins have since been identified from around the world (Norway, Denmark and France). The relative stereochemistry of these compounds has only recently been established via computer calculations and NMR studies. Related marine toxins containing a spiroimine unit have been classified as “fast acting” toxins and the spirolides also target muscarinic and nicotinic acetylcholine receptors and are weak activators of L-type transmembrane Ca²⁺ channels. The spirolides are macrocycles that comprise in two parts: a bis-spiroacetal moiety that has been synthesized by our research group and an unusual 7,6-bicyclic spiroimine which is the putative pharmacophore that has not been synthesized to date.

Type of Paper: Article
Title: Sterol Biosynthesis in the Marine Dinoflagellate, Karenia brevis
Authors: Shannon A. Roche, Nicole M. Porter and Jeffrey D. Leblond
Affiliation: Department of Biology, Middle Tennessee State University, Murfreesboro, TN, USA; E-Mail: jleblond@mtsu.edu
Abstract: Dinoflagellates are a diverse group of photosynthetic and heterotrophic algae that regularly form blooms throughout the world’s oceans and in several of its freshwater bodies. The biosynthesis of sterols, ringed lipids thought to contribute to membrane integrity in eukaryotes, has been elucidated in great detail in yeast and plant/green algae model systems, but is comparatively understudied in dinoflagellates, even though dinoflagellates have been studied for decades as producers of a number of sterols that serve as environmental biomarkers. The objective of this study is therefore to elucidate important biochemical steps in the biosynthesis of brevesterol and gymnodinosterol, the primary biomarker sterols produced by Karenia brevis, by determining structures of selected intermediates that accumulate during exposure to particular fungicides known to inhibit sterol biosynthesis. The fungicides utilized include econazole, an inhibitor of cytochrome P-450-dependent 14α-demethylation of lanosterol and obtusifoliol, intermediates in yeast and plant pathways, respectively, and fenpropidine, an inhibitor of Δ¹⁴-reductase and Δ ^8(9)→7(8) isomerase. This work is thus one of the first forays into understanding biochemical steps in a eukaryotic microbe that is not considered a model organism (such as the well studied yeast and green algal genera Saccharomyces and Chlamydomonas, respectively), yet which greatly impacts human activity.
To date, a small number of peridinin-containing dinoflagellates have been observed to utilize a yeast-like pathway, with lanosterol as a key intermediate (Giner et al. 1991); however, other key intermediates formed en route to production of their normal sterol complement are unknown (there are approximately ten intermediates between cyclization of squalene to formation of end-product sterols). Giner et al. also observed in Kryptoperidinium foliaceum, a dinoflagellate with an aberrant diatom endosymbiont, that both lanosterol and cycloartenol, a key intermediate in the plant sterol biosynthesis pathway, were present. Intermediates in the biosynthesis of brevesterol and gymnodinosterol in the non-peridinin-, aberrant-plastid-containing (potentially of red algal origin) K. brevis are completely unknown.
Our preliminary data suggest, like K. foliaceum, a combination of yeast- and plant-like pathways may be present in K. brevis, even though its plastid ancestry is very different. Exposure of K. brevis to econazole produces an intermediate that resembles lanosterol, two intermediates also observed in econazole-treated yeast and, curiously, an intermediate with a mass spectrum virtually identical to stigmasterol, a common plant sterol that wouldn’t be an expected biosynthetic intermediate en route to brevesterol and gymnodinosterol. Exposure to fenpropidine produces two tri-unsaturated intermediates that appear to be consistent with 14α-demethylation of lanosterol. Characterization of these intermediates and their potential placement within a brevesterol/gymnodinosterol biosynthetic pathway will be presented.

Type of Paper: Review
Title: Biosynthesis and Molecular Genetics of Polyketides in Marine Dinoflagellates
Authors: Ralf Kellmann¹, Anke Stüken^2,3, Russell Orr³, Helene Svendsen¹ and Kjetill S. Jakobsen²
Affiliations: ¹ University of Bergen, Department of Molecular Biology, 5020 Bergen, Norway; E-Mail: ralf.kellmann@mbi.uib.no
² University of Oslo, Department of Biology, Centre for Ecological and Evolutionary Synthesis (CEES), 0316 Oslo, Norway
³ University of Oslo, Department of Biology, Microbial Evolution Research Group (MERG), 0316 Oslo, Norway
Abstract: Marine dinoflagellates are the single most important group of algae that produce toxins, which have a global impact on human activities. The toxins are chemically diverse, and include macrolides, cyclic polyethers, spirolides and purine alkaloids. Whereas there is a multitude of studies describing the pharmacology of these toxins, there is limited or no knowledge regarding the biochemistry and molecular genetics involved in their biosynthesis. Recently, however, exciting advances were made. Expressed sequence tag sequencing studies have revealed important insights into the transcriptomes of dinoflagellates, whereas other studies have implicated polyketide synthase genes in the biosynthesis of cyclic polyether toxins, and the molecular genetic basis for the biosynthesis of paralytic shellfish toxins has been elucidated in cyanobacteria. This review summarises the recent progress that has been made regarding the unusual genomes of dinoflagellates, the biosynthesis and molecular genetics of dinoflagellate toxins. In addition, the evolution of these metabolic pathways will be discussed, and an outlook for future research and possible applications is provided.

Type of Paper: Review
Title: Synthesis of Marine Polycyclic Polyethers via Epoxide-Opening Cascades
Authors: Ivan Vilotijevic and Timothy F. Jamison
Affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02140, USA; E-Mails: vilotije@MIT.EDU (I.V.); tfj@MIT.EDU (T.F.J.)
Abstract: Proposed biosynthetic pathways to ladder polyethers of polyketide origin and oxasqualenoids of terpenoid origin share the dramatic epoxide-opening cascades as their final steps. Polycyclic structures generated in these biosynthetic pathways display biological effects ranging from potentially therapeutic properties to extreme lethality. Much of the structural complexity of ladder polyether and oxasqualenoid natural products can be traced to these hypothesized cascades. In this review we summarize how such epoxide-opening cascade reactions have been used in the synthesis of ladder polyethers and oxasqualenoid natural products.