Natural Products from Cyanobacteria: Focus on Beneficial Activities

Abstract

Cyanobacteria are photosynthetic microorganisms that colonize diverse environments worldwide, ranging from ocean to freshwaters, soils, and extreme environments. Their adaptation capacities and the diversity of natural products that they synthesize, support cyanobacterial success in colonization of their respective ecological niches. Although cyanobacteria are well-known for their toxin production and their relative deleterious consequences, they also produce a large variety of molecules that exhibit beneficial properties with high potential in various fields (e.g., a synthetic analog of dolastatin 10 is used against Hodgkin's lymphoma). The present review focuses on the beneficial activities of cyanobacterial molecules described so far. Based on an analysis of 670 papers, it appears that more than 90 genera of cyanobacteria have been observed to produce compounds with potentially beneficial activities in which most of them belong to the orders Oscillatoriales, Nostocales, Chroococcales, and Synechococcales. The rest of the cyanobacterial orders (i.e., Pleurocapsales, Chroococcidiopsales, and Gloeobacterales) remain poorly explored in terms of their molecular diversity and relative bioactivity. The diverse cyanobacterial metabolites possessing beneficial bioactivities belong to 10 different chemical classes (alkaloids, depsipeptides, lipopeptides, macrolides/lactones, peptides, terpenes, polysaccharides, lipids, polyketides, and others) that exhibit 14 major kinds of bioactivity. However, no direct relationship between the chemical class and the respective bioactivity of these molecules has been demonstrated. We further selected and specifically described 47 molecule families according to their respective bioactivities and their potential uses in pharmacology, cosmetology, agriculture, or other specific fields of interest. With this up-to-date review, we attempt to present new perspectives for the rational discovery of novel cyanobacterial metabolites with beneficial bioactivity.

Keywords: biological activities; chemical classes; cyanobacteria; metabolites; natural products; producers.

Figure 1

Evolution of the cumulative number of metabolite families according to the number of analyzed publications used for the construction of the database. The arrow indicates a reclassification event of all the structural variants of one molecule in a unique entry of “family” [13,25,26]. We observed a progressive stabilization of the number of compound families in the database that supports the postulation of the exhaustiveness of the present database.

Figure 2

Proportion of families of compound by taxonomical level. (A) The pie chart represents the percentage of compound families for each taxonomical family. Note that some compound families can be produced by several cyanobacterial families. The “Other” category concerns other taxonomical families that produce less than two compound families. (B) The histogram shows the number of compound families for each genus. The “Other” category corresponds to genera producing less than four compound families. * indicates cyanobacterial assemblages whom the real metabolite producer is still undetermined. The boxes indicate the environmental origins for the corresponding genera. For both charts, the colors correspond to the taxonomical order of each genus or family.

Figure 3

Classification of the 260 cyanobacterial metabolite families according to their respective chemical classes. All the molecules have been classified into these different classes according to their respective structural characteristics. For example, the depsipeptides are a class of peptides containing an ester bond and macrolides are molecules exhibiting a macrocycle and one or more lactone functions. Some examples of cyanobacterial molecules belonging to these classes are illustrated. Hapalindole A (alkaloids), Oscillapeptin A (depsipeptides), Minutissamide A (lipopeptides), Caylobolide B (macrolides/lactones), Anabaenopeptin E (peptides), β-carotene (terpenes), Cyclodextrin phosphate (polysaccharides), Lyngbic acid (lipids), and Cylindrocyclophane A (polyketides). The main characteristics of each chemical class are highlighted in red. All the structures were obtained from the ChEMBL Database (https://www.ebi.ac.uk/chembl/).

Figure 4

Number of metabolite families observed for each type of activity. The percentage represents the proportion of one activity compared to the whole occurrence of activities detected (n = 362). Some compounds present various activities and are considered several times.

Figure 5

Classification of the 260 metabolite families according to their respective activities and chemical classes. The number of metabolite families is symbolized by the disc diameters, for each activity and each chemical class. For example, the first circle represents the number of alkaloids that exhibit a hepatotoxic activity (in this case, one family of metabolites). Colors correspond to the different categories of activity targets. For example, cytotoxicity and hepatotoxicity are tested in vitro against cell lines while neurotoxicity, antioxidant, and anti-inflammatory activities can be biochemically tested for specific cellular mechanisms (such as the sodium influx, the scavenging of ROS (reactive oxygen species), and the inhibition of cytokines).