https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

(2002). The Effects of Harmful Algal Blooms on Aquatic Organisms. Reviews in Fisheries Science: Vol. 10, No. 2, pp. 113-390.

The Effects of Harmful Algal Blooms on Aquatic Organisms

3.3.1. Potential of the “Metagenome” 3016 3.3.2. Cryptic Clusters in Bacteria and Fungi 3016 3.3.3. Cyanophytes 3017 3.3.4. Marine Microbes (Non-Cyanophytes) 3018 3.3.5. Extremophiles 3018 3.3.6. Microbial Symbionts 3019 3.3.7. Plant Endophytes 3020 3.3.8. Combinatorial Biosynthesis 3020 4. Development of Drugs from Natural Products 3020 4.1. Synthesis Based on Natural Products 3021 4.1.1. Derivatization and Semisynthesis 3021 4.1.2. Total Synthesis 3021 4.1.3. Diverted Total Synthesis 3021 4.2. Natural Product-Inspired Combinatorial Synthesis 3022

Impact of natural products on developing new anti-cancer agents

Marine cyanobacteria—a prolific source of natural products

Cyanobacterial secondary metabolites have attracted increasing scientific interest due to bioactivity of many compounds in various test systems. Among the known structures, oligopeptides are often found with many congeners sharing conserved substructures, while being highly variable in others. A major part of known oligopeptides are of non-ribosomal origin and can be grouped into classes with conserved structural properties. Thus, the overall structural diversity of cyanobacterial oligopeptides only seemingly suggests an equally high diversity of biosynthetic pathways and respective genes. For each class of peptides, some of which have been found in all major branches of the cyanobacterial evolutionary tree, homologous synthetases and genes can be inferred. This implies that non-ribosomal peptide synthetase genes are a very ancient part of the cyanobacterial genome and presumably have evolved by recombination and duplication events to reach the present structural diversity of cyanobacterial oligopeptides. In addition, peptide synthetases would appear to be an essential part of the cyanobacterial evolution and physiology. The present review presents an overview of the biosynthesis of cyanobacterial peptides and corresponding gene clusters, the structural diversity of structural types and structural variations within peptide classes, and implications for the evolution and plasticity of biosynthetic genes and the potential function of cyanobacterial peptides.

Cyanobacterial peptides – Nature's own combinatorial biosynthesis

Bioassay-guided fractionation of the organic extract of a Curacao collection of Lyngbya majuscula led to the isolation of a new lipid, curacin A, with exceptional brine shrimp toxic and antiproliferative activities. Its unique thiazoline-containing structure has been deduced from spectroscopic information. Pure curacin A is an antimitotic agent (IC 50 values in three cell lines ranging from 7 to 200 nM) that inhibits microtubule assembly and the binding of colchicine to tubulin

Structure of Curacin A, a Novel Antimitotic, Antiproliferative and Brine Shrimp Toxic Natural Product from the Marine Cyanobacterium Lyngbya majuscula

Curacin A, the major lipid constituent of a strain of the marine cyanobacterium Lyngbya majuscula obtained off the coast of Curacao, is a potent antimitotic agent that we have previously shown to inhibit microtubule assembly and colchicine binding to tubulin. In the present study, we report that curacin A probably binds in the colchicine site because it competitively inhibits the binding of [3H]colchicine to tubulin with an apparent Ki value of 0.6 microM and stimulates tubulin-dependent GTP hydrolysis, as do most other colchicine-site agents. The binding of curacin A to tubulin resembled the binding reactions of combretastatin A-4 and podophyllotoxin in contrast to that of colchicine in that it occurred as extensively on ice as at higher temperatures. However, once bound, the dissociation rate of curacin A from tubulin is very slow, more closely resembling that observed with colchicinoids (thiocolchicine was the drug examined) than the faster dissociation that occurs with combretastatin A-4 and podophyllotoxin. Because the molecular structure of curacin A is so different from that of previously described colchicine-site drugs (e.g., there is no aromatic moiety, and there are only two conjugated double bonds in its linear hydrocarbon chain), we have been examining the activities of natural isomers and synthetic derivatives. So far, only modest enhancement or reduction of activity has been observed with a variety of structural changes.

Characterization of the interaction of the marine cyanobacterial natural product curacin A with the colchicine site of tubulin and initial structure-activity studies with analogues.

Curacin A is a newly isolated lipid natural product that binds in the colchicine site of tubulin and inhibits mitosis. We have examined its effects on tubulin polymerization, studied by turbidimetry, under three reaction conditions. In 1.0 M glutamate + 1.0 mM MgCl2, with a 37°C reaction temperature, we could find no concentration of curacin A that completely inhibited polymerization. A maximal inhibitory effect on turbidity development (about 50%) was observed with 5 mM drug. Higher drug concentrations induced an abnormal polymerization reaction, which at 40 mM differed little from the control reaction except for slightly delayed depolymerization in response to reducing the temperature to 0°C. In 0.8 M glutamate (no MgCl2), with a 30°C reaction temperature, complete inhibition did occur at 3–5 mM drug, but higher drug concentrations again induced an abnormal polymerization reaction. With 40 mM curacin A this reaction was also similar to the control reaction, except that cold-induced depolymerization was slightly enhanced relative to the control. When polymerization was induced by microtubule-associated proteins, maximal inhibition of turbidity development (about 70%) occurred with 2 mM drug, with higher curacin A concentrations inducing abnormal polymerization reactions that reached about 60% of the control turbidity readings. Under all three reaction conditions the polymer induced by high concentrations of curacin A consisted of large aggregates of tightly coiled spiral fibers that had a 2–3 filament substructure. The implications of these findings with curacin A are discussed in terms of the use of tubulin polymerization assays as a screen for identifying new antimitotic drugs. © 1995 Wiley-Liss, Inc.1

Limitations in the use of tubulin polymerization assays as a screen for the identification of new antimitotic agents: The potent marine natural product curacin A as an example

Evidence for a distinct ligand binding site on tubulin discovered through inhibition by GDP of paclitaxel-induced tubulin assembly in the absence of exogenous GTP

Andrei V. Blokhin

Papers

Structure of Curacin A, a Novel Antimitotic, Antiproliferative and Brine Shrimp Toxic Natural Product from the Marine Cyanobacterium Lyngbya majuscula

Characterization of the interaction of the marine cyanobacterial natural product curacin A with the colchicine site of tubulin and initial structure-activity studies with analogues.

Limitations in the use of tubulin polymerization assays as a screen for the identification of new antimitotic agents: The potent marine natural product curacin A as an example

Evidence for a distinct ligand binding site on tubulin discovered through inhibition by GDP of paclitaxel-induced tubulin assembly in the absence of exogenous GTP