The cyanobacteria or “blue-green algae”, as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites.

Summary Over the past 15 years, the genetic basis for production of many cyanobacterial bioactive compounds has been described. This knowledge has enabled investigations into the environmental factors that regulate the production of these toxins at the molecular level. Such molecular or systems level studies are also likely to reveal the physiological role of the toxin and contribute to effective water resource management. This review focuses on the environmental regulation of some of the most relevant cyanotoxins, namely the microcystins, nodularin, cylindrospermopsin, saxitoxins, anatoxins and jamaicamides.

The cyanobacterium Microcystis aeruginosa is widely known for its production of the potent hepatotoxin microcystin. Microcystin is synthesized nonribosomally by the thiotemplate function of a large, modular enzyme complex encoded within the 55-kb microcystin synthetase (mcy) gene cluster. Also encoded within the mcy gene cluster is a putative ATP binding cassette (

No abstract

NtcA is a transcription factor that has been found in a diverse range of cyanobacteria. This nitrogencontrolled factor was focused on as a key component in the yet-to-be-deciphered regulatory network controlling microcystin production. Adaptor-mediated PCR was utilized to isolate the ntcA gene from Microcystis aeruginosa PCC 7806 is a bloom-forming unicellular photosynthetic cyanobacterium that is capable of producing the hepatotoxin microcystin. Investigations of the role and function of microcystin are ongoing, as the true nature of this toxin has not been determined yet. Cyanobacteria have developed adaptive mechanisms that enable them to survive in a vast range of habitats, and their wide distribution and diversity, coupled with the accelerating frequency and intensity of toxic blooms, have sustained interest in this field

No abstract

No abstract

Mycosporine-like amino acids (MAAs) are an important class of secondary metabolites known for their protection against UV radiation and other stress factors. Cyanobacteria produce a variety of MAAs, including shinorine, the active ingredient in many sunscreen creams. Bioinformatic analysis of the genome of the soil-dwelling cyanobacterium Cylindrospermum stagnale PCC 7417 revealed a new gene cluster with homology to MAA synthase from Nostoc punctiforme. This newly identified gene cluster is unusual because it has five biosynthesis genes (mylA to mylE), compared to the four found in other MAA gene clusters. Heterologous expression of mylA to mylE in Escherichia coli resulted in the production of mycosporine-lysine and the novel compound mycosporine-ornithine. To our knowledge, this is the first time these compounds have been heterologously produced in E. coli and structurally characterized via direct spectral guidance. This study offers insight into the diversity, biosynthesis, and structure of cyanobacterial MAAs and highlights their amenability to heterologous production methods. M ycosporine-like amino acids (MAAs) are commonly found in marine microbes exposed to high levels of UV radiation, including aquatic fungi, eukaryotic algae, and cyanobacteria (1-6). These small (Ͻ400 Da), colorless, water-soluble compounds are composed of a 4-deoxygadusol core conjugated with an amino acid or alcohol (7). Their absorption maxima typically range from 310 to 360 nm and their molar extinction coefficients (ε) range from 28,100 to 50,000 M Ϫ1 cm Ϫ1 (8, 9). Commonly termed "microbial sunscreens," MAAs can dissipate UV energy as heat without generating free oxygen radicals (7).While UV exposure is necessary to elicit the synthesis of MAAs (10), some studies suggest that other factors, including osmotic stress, may also be involved in MAA regulation (11). Indeed, MAAs are widely considered to be multifunctional compounds offering protection against oxidative, osmotic, and thermal stress as well as UV radiation (12-17). However, this may not be true for all MAAs (11). Due to their diverse biological properties, MAAs are promising candidates for pharmaceutical and cosmetic applications (3, 18). For example, shinorine, produced by the cyanobacterium Anabaena variabilis, has already been commercialized as an active ingredient in sunscreen creams (Helioguard 365 and Helionori) (14).The biosynthesis of shinorine ( Fig. 1) was recently elucidated via heterologous expression in Escherichia coli (19,20) and is a model pathway for MAA biosynthesis. In A. variabilis ATCC 29413, the shinorine biosynthesis gene cluster consists of four genes: ava_3855 to ava_3858. The first step in the biosynthesis of shinorine is the conversion of sedoheptulose-7-phosphate (SH-7P) to 2-demethyl-4-deoxygadusol (DDG) by a DDG synthase (Ava_3858). Following this, DDG is converted to the mycosporine core compound 4-deoxygadusol (4-DG) by an O-methyltransferase (O-MT) (Ava_3857). Glycylation of 4-DG is catalyzed by a C-N ligase (Ava_3856), resulting ...