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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.

Blooms of planktonic cyanobacteria have long been of concern in lakes, but more recently, harmful impacts of riverine benthic cyanobacterial mats been recognized. As yet, we know little about how various benthic cyanobacteria are distributed in river networks, or how environmental conditions or other associated microbes in their consortia affect their biosynthetic capacities. We performed metagenomic sequencing for 22 Oscillatoriales-dominated (Cyanobacteria) microbial mats collected across the Eel River network in Northern California and investigated factors associated with anatoxin-a producing cyanobacteria. All microbial communities were dominated by one or two cyanobacterial species, so the key mat metabolisms involve oxygenic photosynthesis and carbon oxidation. Only a few metabolisms fueled the growth of the mat communities, with little evidence for anaerobic metabolic pathways. We genomically defined four cyanobacterial species, all which shared <96% average nucleotide identity with reference Oscillatoriales genomes and are potentially novel species in the genus Microcoleus . One of the Microcoleus species contained the anatoxin-a biosynthesis genes, and we describe the first anatoxin-a gene cluster from the Microcoleus clade within Oscillatoriales. Occurrence of these four Microcoleus species in the watershed was correlated with total dissolved nitrogen and phosphorus concentrations, and the species that contains the anatoxin-a gene cluster was found in sites with higher nitrogen concentrations. Microbial assemblages in mat samples with the anatoxin-a gene cluster consistently had a lower abundance of Burkholderiales (Betaproteobacteria) species than did mats without the anatoxin-producing genes. The associations of water nutrient concentrations and certain co-occurring microbes with anatoxin-a producing Microcoleus motivate further exploration for their roles as potential controls on the distributions of toxigenic benthic cyanobacteria in river networks.

Despite the global significance of cyanobacteria, their taxonomy is still heavily lagging behind the progress in genome sequencing. Besides nomenclatural issues and difficulties in species identification, this problem is largely a consequence of missing reference strains and sequences for many cyanobacterial taxa. In this study, a robust multilocus phylogenetic tree based on 23 conserved proteins from the current set of available genomes is presented and compared to a respective 16S rRNA gene tree. To facilitate further progress in achieving a stable system of monophyletic taxa, the phylogenetic status of eight cyanobacterial orders recently proposed in the botanical system was evaluated. While several orders addressed by previous studies (Gloeobacterales, Spirulinales, Chroococcidiopsidales, Nostocales) retain their monophyly, the remaining big groups (Synechococcales, Pleurocapsales, Chroococcales, Oscillatoriales) are polyphyletic and require thorough revision. Comparison of the 16S rRNA tree to the multilocus tree supports the careful use of this gene in distinguishing cyanobacterial genera, whereas its application at other taxonomic levels is limited.

Nature-based and sustainably sourced cosmetics have been dominating the area of skincare products worldwide. Due to their antioxidant and antiaging properties, compounds from cyanobacteria, such as carotenoids and phycobiliproteins, may replace synthetic ingredients in cosmetic formulations and may be used in products such as sunscreens, skincare creams, and makeup. In this study, we evaluated the potential of acetonic and aqueous extracts from cyanobacteria strains of the genera Cyanobium and Leptothoe and from strains within Synechococcales and Oscillatoriales orders, for use in cosmetics. Extractions were sequentially performed with acetone and water. Extracts were firstly analyzed for their toxicity to keratinocytes, fibroblasts, and endothelial cells (HaCAT, 3T3L1 and hCMEC/D3, respectively). The non-cytotoxic extracts were characterized in terms of total proteins, carotenoids, chlorophyll, phenols, phycobiliproteins, and analyzed for their antioxidant potential against the superoxide anion radical (O2•−), and for their ability to inhibit key enzymes associated with the skin aging process. Aqueous extracts were richer in total proteins and phycobiliproteins. The aqueous extracts of Synechococcales cyanobacterium LEGE 181157 and Synechococcales cyanobacterium LEGE 181150 showed the highest value for total proteins (760.81 and 695.25 μg BSA mL−1dry extract, respectively) and the best values regarding O2•− scavenging (IC50 = 63.24 and 112.18 μg mL−1dry extract, respectively) with a significant negative correlation observed (p < 0.01). Moreover, aqueous extracts of Synechococcales cyanobacterium LEGE 181150 and Synechococcales cyanobacterium LEGE 181157 inhibited hyaluronidase, (IC50 of 483.86 and 645.06 μg mL−1dry extract, respectively), with a significant negative correlation with total proteins (p < 0.05), pointing out the contribution of these compounds to the biological activities observed. Acetonic extracts were richer in carotenoids and phenols. Zeaxanthin and β-carotene were predominant among all strains, being present in higher amount in Cyanobium sp. LEGE 07175 (53.08 μg mg−1) and Leptothoe sp. LEGE 181156 (47.89 μg mg−1), respectively. The same strains also showed the highest values for collagenase inhibition at 750 μg mL−1dry extract (32.88 and 36.61%, respectively). Furthermore, Leptothoe sp. LEGE 181156 exhibited the lowest IC50 value for tyrosinase inhibition (465.92 μg mL−1dry extract) and Synechococcales cyanobacterium LEGE 181157 presented the best values for elastase inhibition (IC50 of 380.50 and IC25 of 51.43 μg mL−1dry extract). In general, cyanobacteria extracts demonstrated potential for being used for antiaging purposes, with aqueous extracts being more efficient at free radicals scavenging and acetonic ones at avoiding degradation of dermal matrix components.

Diet in fish is influenced by multiple factors including nutritional requirements, trophic morphology and spatial and temporal variation in resource availability. We examined spatial variation in trophic resources on substrata grazed by scarinine parrotfishes by combining quantitative microhistology with 16S and 18S small subunit rRNA barcoding of feeding substrata in six parrotfish species on outer-shelf reefs of the Great Barrier Reef, Australia. We then compared four of these taxa with conspecific data from mid-shelf reefs differing in incident wave energy, parrotfish assemblage structure and benthic cover of hard corals, crustose coralline algae (CCA) and macroalgae. The dominant biota on outer-shelf feeding substrata in terms of both surface coverage and frequency of occurrence were filamentous cyanobacteria. The density of filamentous cyanobacteria on outer-shelf feeding substrata as measured by microscope did not differ either among the six parrotfish species or within-species cross-shelf. Endolithic and epilithic filamentous cyanobacteria from the order Nostocales were the most frequently observed filamentous cyanobacteria, suggesting that these represent a key feeding target for these parrotfishes. In addition to filamentous Nostocales cyanobacteria, taxa that were consistently present on both mid-shelf and outer-shelf feeding substrata were the euendolithic micro-chlorophytes Ostreobium and Phaeophila, diatoms, fungi, CCA, Peyssonnelia, dinoflagellates of the family Symbiodiniaceae, the sponge taxa Clionaida and Poecilosclerida and the filamentous algae Sphacelaria and Polysiphonia. Our results reveal key nutritional drivers underlying feeding by parrotfish on carbonate reefs and provide further support for the hypothesis that microscopic photoautotrophs are a major dietary target for grazing parrotfishes.

Dysidazirine carboxylic acid (1) was isolated from the lipophilic extract of a collection of the benthic marine cyanobacterium Caldora sp. from reefs near Fort Lauderdale, Florida. The planar structure of this new compound was determined by spectroscopic methods and comparisons between HRMS and NMR data with its reported methyl ester. The absolute configuration of the single chiral center was determined by the conversion of 1 to the methyl ester and the comparison of its specific rotation data with the two known methyl ester isomers, 2 and 3. Molecular sequencing with 16S rDNA indicated that this cyanobacterium differs from Caldora penicillata (Oscillatoriales) and represents a previously undocumented and novel Caldora species. Dysidazirine (2) showed weak cytotoxicity against HCT116 colorectal cancer cells (IC50 9.1 µM), while dysidazirine carboxylic acid (1) was non-cytotoxic. Similar cell viability patterns were observed in RAW264.7 cells with dysidazirine only (2), displaying cytotoxicity at the highest concentration tested (50 µM). The non-cytotoxic dysidazirine carboxylic acid (1) demonstrated anti-inflammatory activity in RAW264.7 cells stimulated with LPS. After 24 h, 1 inhibited the production of NO by almost 50% at 50 µM, without inducing cytotoxicity. Compound 1 rapidly decreased gene expression of the pro-inflammatory gene iNOS after 3 h post-LPS treatment and in a dose-dependent manner (IC50 ~1 µM); the downregulation of iNOS persisted at least until 12 h.

Phormidium lacuna is a naturally competent, filamentous cyanobacterium that belongs to the order Oscillatoriales. The filaments are motile on agar and other surfaces and display rapid lateral movements in liquid culture. Furthermore, they exhibit a photophobotactic response, a phototactic response towards light that is projected vertically onto the area covered by the culture. However, the molecular mechanisms underlying these phenomena are unclear. We performed the first molecular studies on the motility of an Oscillatoriales member. We generated mutants in which a kanamycin resistance cassette (KanR) was integrated in the phytochrome gene cphA and in various genes of the type IV pilin apparatus. pilM , pilN , pilQ and pilT mutants were defective in gliding motility, lateral movements and photophobotaxis, indicating that type IV pili are involved in all three kinds of motility. pilB mutants were only partially blocked in terms of their responses. pilB is the proposed ATPase for expelling of the filament in type IV pili. The genome reveals proteins sharing weak pilB homology in the ATPase region, these might explain the incomplete phenotype. The cphA mutant revealed a significantly reduced photophobotactic response towards red light. Therefore, our results imply that CphA acts as one of several photophobotaxis photoreceptors or that it could modulate the photophobotaxis response.

In the published article, there was an error. The introduction to this manuscript includes a typographical error which misstates the maximum salinity and pH previously observed in related cyanobacterial species. This error does not impact any analyses or conclusions reached in this manuscript.

Cyanobacteria are among the most diverse morphological microorganisms that inhabit a great variety of habitats. Their presence in the Azores, a volcanic archipelago of nine islands in the middle of the North Atlantic Ocean, has already been reported. However, due to the high diversity of cyanobacteria habitats, their biodiversity is still understudied, mainly in extreme environments. To address this, a total of 156 cyanobacteria strains from Azores lakes, streams, thermal and terrestrial habitats were isolated. Identification was made based on a polyphasic approach using classical taxonomy (morphological characteristics and environmental data) and phylogeny among 81 strains assessed by maximum likelihood and Bayesian analysis of 16S rDNA partial sequences. The 156 isolates showed a high genera diversity (38) belonging to the orders Chroococcales, Nostocales, Oscillatoriales, and Synechococcales. Eleven new genera for the Azores habitats are here reported, reinforcing that cyanobacteria biodiversity in these islands is still much understudied. Phylogenetic analysis showed 14 clusters associated with these cyanobacteria orders, with evidence for six new genera and valuable information towards Microchaete/Coleospermum taxonomic revision that better reflects species environmental distribution. These results emphasize the need for cyanobacteria taxonomy revisions, through polyphasic studies, mainly in Synechococcales order and in the Microchaete/Coleospermum, Nostoc, and Anabaena genera.

Microcystis aeruginosa is a major harmful cyanobacterium causing water bloom worldwide. Cyanophage has been proposed as a promising tool for cyanobacterial bloom. In this study, M. aeruginosa FACHB-1326 was used as an indicator host to isolate cyanophage from Lake Taihu. The isolated Microcystis cyanophage Mae-Yong1326-1 has an elliptical head of about 47 nm in diameter and a slender flexible tail of about 340 nm in length. Mae-Yong1326-1 could lyse cyanobacterial strains across three orders (Chroococcales, Nostocales, and Oscillatoriales) in the host range experiments. Mae-Yong1326-1 was stable in stability tests, maintaining high titers at 0–40 °C and at a wide pH range of 3–12. Mae-Yong 1326-1 has a burst size of 329 PFU/cell, which is much larger than the reported Microcystis cyanophages so far. The complete genome of Mae-Yong1326-1 is a double-stranded DNA of 48, 822 bp, with a G + C content of 71.80% and long direct terminal repeats (DTR) of 366 bp, containing 57 predicted ORFs. No Mae-Yong1326-1 ORF was found to be associated with virulence factor or antibiotic resistance. PASC scanning illustrated that the highest nucleotide sequence similarity between Mae-Yong1326-1 and all known phages in databases was only 17.75%, less than 70% (the threshold to define a genus), which indicates that Mae-Yong1326-1 belongs to an unknown new genus. In the proteomic tree based on genome-wide sequence similarities, Mae-Yong1326-1 distantly clusters with three unclassified Microcystis cyanophages (MinS1, Mwe-Yong1112-1, and Mwes-Yong2). These four Microcystis cyanophages form a monophyletic clade, which separates at a node from the other clade formed by two independent families (Zierdtviridae and Orlajensenviridae) of Caudoviricetes class. We propose to establish a new family to harbor the Microcystis cyanophages Mae-Yong1326-1, MinS1, Mwe-Yong1112-1, and Mwes-Yong2. This study enriched the understanding of freshwater cyanophages.