Submit to Special Issue Submit Abstract to Special Issue Review for Marine Drugs Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Special Issue "Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins"

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Toxins".

Deadline for manuscript submissions: 31 December 2023 | Viewed by 6945

Share This Special Issue

Special Issue Editor

Prof. Dr. Kathleen S. Rein

E-Mail Website
Guest Editor

Departments of Marine and Earth Science and Chemistry and Physics, The Water School, Florida Gulf Coast University, 10501 FGCU Boulevard South, Fort Myers, FL 33965, USA
Interests: algal toxins; chemistry; toxicology; pharmacology; biosynthesis; metabolism; endogenous function; biological receptors

Special Issue Information

Dear Colleagues,

Throughout the world, toxins produced by marine algae and cyanobacteria pose a threat to humans, wildlife, local ecosystems and local economies. This Special Issue welcomes manuscripts related to the chemistry and biochemistry of marine algal toxins. This includes the identification and characterization of new toxins, including novel structures and modifications of known scaffolds. Algal toxins represent a chemically diverse collection of molecules and as such the biological targets are equally varied. Contributions related to refinements in our understanding of the interactions of toxins and their known biological receptors at the molecular level as well as the identification of new or secondary biological receptors and downstream outcomes or pathway activation are welcomed. Few treatments for poisonings with algal toxins are known and studies on mechanism-based interventions, antagonists or anti-toxins are needed. More often than not, the endogenous role that algal toxins play in producing organisms is not well understood and contributions that involve the identification of endogenous biological receptors or biological function are encouraged. The biosynthetic pathways for the production of algal toxins can be complex and sometimes enigmatic. Novel approaches, such as proteomics, metabolomics or transcriptomics, towards the understanding of some of these seemingly inscrutable biological pathways are welcomed. Finally, studies related to the metabolism of marine algal toxins including microbial degradation pathways would be of interest.

Prof. Dr. Kathleen S. Rein
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

algal toxins
structure elucidation
pharmacology
toxicology
mechanism of action
mechanism-based treatments
biological targets
biosynthesis
metabolism
microbial degradation

Published Papers (6 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

19 pages, 6334 KiB

Open AccessArticle

Investigating A Multi-Domain Polyketide Synthase in Amphidinium carterae

and

Mar. Drugs 2023, 21(8), 425; https://doi.org/10.3390/md21080425 - 27 Jul 2023

Viewed by 871

Abstract

Dinoflagellates are unicellular organisms that are implicated in harmful algal blooms (HABs) caused by potent toxins that are produced through polyketide synthase (PKS) pathways. However, the exact mechanisms of toxin synthesis are unknown due to a lack of genomic segregation of fat, toxins, and other PKS-based pathways. To better understand the underlying mechanisms, the actions and expression of the PKS proteins were investigated using the toxic dinoflagellate Amphidinium carterae as a model. Cerulenin, a known ketosynthase inhibitor, was shown to reduce acetate incorporation into all fat classes with the toxins amphidinol and sulpho-amphidinol. The mass spectrometry analysis of cerulenin-reacted synthetic peptides derived from ketosynthase domains of A. carterae multimodular PKS transcripts demonstrated a strong covalent bond that could be localized using collision-induced dissociation. One multi-modular PKS sequence present in all dinoflagellates surveyed to date was found to lack an AT domain in toxin-producing species, indicating trans-acting domains, and was shown by Western blotting to be post-transcriptionally processed. These results demonstrate how toxin synthesis in dinoflagellates can be differentiated from fat synthesis despite common underlying pathway. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

17 pages, 4588 KiB

Open AccessArticle

Brevetoxin versus Brevenal Modulation of Human Nav1 Channels

Rocio K. Finol-Urdaneta

Boris S. Zhorov

Daniel G. Baden

and

David J. Adams

Mar. Drugs 2023, 21(7), 396; https://doi.org/10.3390/md21070396 - 07 Jul 2023

Cited by 2 | Viewed by 764

Abstract

Brevetoxins (PbTx) and brevenal are marine ladder-frame polyethers. PbTx binds to and activates voltage-gated sodium (Nav) channels in native tissues, whereas brevenal antagonizes these actions. However, the effects of PbTx and brevenal on recombinant Nav channel function have not been systematically analyzed. In this study, the PbTx-3 and brevenal modulation of tissue-representative Nav channel subtypes Nav1.2, Nav1.4, Nav1.5, and Nav1.7 were examined using automated patch-clamp. While PbTx-3 and brevenal elicit concentration-dependent and subtype-specific modulatory effects, PbTx-3 is >1000-fold more potent than brevenal. Consistent with effects observed in native tissues, Nav1.2 and Nav1.4 channels were PbTx-3- and brevenal-sensitive, whereas Nav1.5 and Nav1.7 appeared resistant. Interestingly, the incorporation of brevenal in the intracellular solution caused Nav channels to become less sensitive to PbTx-3 actions. Furthermore, we generated a computational model of PbTx-2 bound to the lipid-exposed side of the interface between domains I and IV of Nav1.2. Our results are consistent with competitive antagonism between brevetoxins and brevenal, setting a basis for future mutational analyses of Nav channels’ interaction with brevetoxins and brevenal. Our findings provide valuable insights into the functional modulation of Nav channels by brevetoxins and brevenal, which may have implications for the development of new Nav channel modulators with potential therapeutic applications. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

12 pages, 1326 KiB

Open AccessArticle

Discovering a New Okadaic Acid Derivative, a Potent HIV Latency Reversing Agent from Prorocentrum lima PL11: Isolation, Structural Modification, and Mechanistic Study

and

Mar. Drugs 2023, 21(3), 158; https://doi.org/10.3390/md21030158 - 27 Feb 2023

Viewed by 1110

Abstract

Marine toxins (MTs) are a group of structurally complex natural products with unique toxicological and pharmacological activities. In the present study, two common shellfish toxins, okadaic acid (OA) (1) and OA methyl ester (2), were isolated from the cultured microalgae strain Prorocentrum lima PL11. OA can significantly activate the latent HIV but has severe toxicity. To obtain more tolerable and potent latency reversing agents (LRAs), we conducted the structural modification of OA by esterification, yielding one known compound (3) and four new derivatives (4–7). Flow cytometry-based HIV latency reversal activity screening showed that compound 7 possessed a stronger activity (EC₅₀ = 46 ± 13.5 nM) but was less cytotoxic than OA. The preliminary structure–activity relationships (SARs) indicated that the carboxyl group in OA was essential for activity, while the esterification of carboxyl or free hydroxyls were beneficial for reducing cytotoxicity. A mechanistic study revealed that compound 7 promotes the dissociation of P-TEFb from the 7SK snRNP complex to reactivate latent HIV-1. Our study provides significant clues for OA-based HIV LRA discovery. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

19 pages, 2027 KiB

Open AccessArticle

Rapid Biotic and Abiotic Transformation of Toxins produced by Ostreopsis. cf. ovata

and

Mar. Drugs 2022, 20(12), 748; https://doi.org/10.3390/md20120748 - 28 Nov 2022

Viewed by 1357

Abstract

The dinoflagellate Ostreopsis cf. ovata produces several families of toxic polyketides. Despite only a few field measurements of these phycotoxins in seawater and aerosols, they are believed to be responsible for dermatitis and the toxic inhalations reported during blooms of this species. Therefore, the stability of these compounds in seawater is essential to understanding the causes of these symptoms, however, this has never been assessed. In the current study, the optimization of a solid phase extraction (SPE) procedure was first performed to ensure the most efficient extraction of all phycotoxins known to be produced by this strain, including the recently described liguriatoxins. The SPE cartridge SDBL^® under non acidified conditions offered the best option. The stability of the ovatoxins and the liguriatoxins under biotic and abiotic stress was assessed by exposing the spent medium of a culture of Ostreopsis cf. ovata to its bacterial consortium and natural sunlight. A rapid biotic transformation was detected for both families of compounds. When exposed to bacteria, the half-lives of the ovatoxins were reached before 10 h and at 36 h, 97% of these toxins had been transformed. The half-lives of the liguriatoxins were 10 h under these conditions. Photolysis (abiotic degradation) of the ovatoxins (T_1/2 < 36 h) was faster than for the liguriatoxins (T_1/2 > 62 h). Although none of the catabolites of these phycotoxins were thoroughly identified, an untargeted metabolomics approach combined with molecular networking highlighted the presence of several compounds exhibiting structural similarities with the ovatoxins. Additional work should confirm the preliminary findings on these potential ovatoxins’ catabolites and their biological properties. The rapid transformation of O. cf. ovata’s phycotoxins introduces questions concerning their presence in seawater and their dispersion in the sea spray aerosols. The compounds involved in the toxic inhalations and dermatitis often experienced by beachgoers may stem from the catabolites of these toxins or even unrelated and as yet unidentified compounds. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

19 pages, 5611 KiB

Open AccessArticle

A Comparison of Dinoflagellate Thiolation Domain Binding Proteins Using In Vitro and Molecular Methods

Ernest Williams

Tsvetan Bachvaroff

and

Allen Place

Mar. Drugs 2022, 20(9), 581; https://doi.org/10.3390/md20090581 - 18 Sep 2022

Cited by 1 | Viewed by 1166

Abstract

Dinoflagellates play important roles in ecosystems as primary producers and consumers making natural products that can benefit or harm environmental and human health but are also potential therapeutics with unique chemistries. Annotations of dinoflagellate genes have been hampered by large genomes with many gene copies that reduce the reliability of transcriptomics, quantitative PCR, and targeted knockouts. This study aimed to functionally characterize dinoflagellate proteins by testing their interactions through in vitro assays. Specifically, nine Amphidinium carterae thiolation domains that scaffold natural product synthesis were substituted into an indigoidine synthesizing gene from the bacterium Streptomyces lavendulae and exposed to three A. carterae phosphopantetheinyl transferases that activate synthesis. Unsurprisingly, several of the dinoflagellate versions inhibited the ability to synthesize indigoidine despite being successfully phosphopantetheinated. However, all the transferases were able to phosphopantetheinate all the thiolation domains nearly equally, defying the canon that transferases participate in segregated processes via binding specificity. Moreover, two of the transferases were expressed during growth in alternating patterns while the final transferase was only observed as a breakdown product common to all three. The broad substrate recognition and compensatory expression shown here help explain why phosphopantetheinyl transferases are lost throughout dinoflagellate evolution without a loss in a biochemical process. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 5841 KiB

Open AccessReview

Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

and

Mar. Drugs 2023, 21(4), 217; https://doi.org/10.3390/md21040217 - 29 Mar 2023

Cited by 1 | Viewed by 1130

Abstract

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Journal Menu

Journal Browser

Special Issue "Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins"

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (6 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI