**2.3. Alkaloids**

of secondary metabolites can be produced according to the stress environment with a high degree of structural variation across the different compound classes. These suites of metabolites include; peptides, polyketides, alkaloids, terpenoids and UV-absorbing (**Figure 1**). Accordingly they possess a wide variety of functions to protect the cells such as; defence against predators and grazers, chemosensory, photoprotection and antioxidant roles. These properties can

be utilized in industrial biotechnology as nutraceuticals, cosmeceuticals and pharmaceuticals.

**2. Cyanobacterial secondary metabolites by chemical structure and** 

tumour promoting activity by activation of protein kinase C (PKC) [11].

receptors and is biosynthesised from L-proline using three PKS modules [9].

potential as a lead compound for the treatment of cancer due to its cytotoxicity [13].

Commonly occurring as secondary metabolites in cyanobacteria are nonribosomal peptides NRPs. These are produced using specialised nonribosomal peptide synthases (NRPS). NRPS contains modules, which are responsible for integrating specific amino acids into peptide chains. These modules consist of an adenylation domain, peptidyl carrier domain and a condensation domain, which incorporates proteinogenic and nonproteinogenic amino acids. Other domains can also be present for further modifications such as N-methylation, epimerization and cyclisation of the amino acid backbone, which gives rise to the intricate chemical structures produced [9]. Lyngbyatoxins, such as lyngbyatoxin-a (**Figure 1 (1)**), are biosynthesised *via* NRPS pathway in *Lyngbya majuscule* and comprise of an indolactam ring composed of L-valine, L-tryptophan and methionine [10]. Lyngbyatoxin-a is a dermatoxin with potent

Another large class of secondary metabolites found in cyanobacteria are the polyketides, which are biosynthesised from acetyl-CoA using polyketide synthases (PKS). Similarly to NRPS, PKS modules consist of a acyltransferase domain, acyl carrier protein domain and ketosynthase domain as well as additional domains for further modification [12]. The neurotoxin anatoxin-a (**Figure 1 (2)**) from *Anabaena* sp. Binds irreversibly to nicotinic acetylcholine

Hybrid metabolites are primarily derived from the attachment of polyketide or fatty acids using PKS to nonribosomal peptides in a natural combinatorial biosynthetic pathway to produce an array of chemical structures with specific roles and bioactivity. Microcystin-LR (**Figure 1 (3)**) is biosynthesised using multi-enzymes of NRPS and PKS modules and has

Ribosomal peptides (RPs) are synthesised on the ribosome and only use proteinogenic amino acid. They are similar to NRPs due to their posttranslational modifications. A prevalent group of ribosomal peptides found in cyanobacteria are the cyanobactin. These are cyclic and less commonly linear peptides formed through the post-ribosomal peptide synthesis (PRPS) pathway, which then undergoes post modifications to form their final complex structures [14],

**biosynthesis**

**2.2. Ribosomal peptides**

**2.1. Nonribosomal peptides and polyketides**

26 Secondary Metabolites - Sources and Applications

Alkaloids are nitrogen containing natural compounds, which usually have toxic properties, an example includes the saxitoxins also known as paralytic shellfish poisons (**Figure 1 (6)**), which are neurotoxins found in a number of cyanobacteria [15].

Indole alkaloids are a class of alkaloids containing an indole moiety such as the hapalindoles (hapalindole-A, **Figure 1 (7)**), hapalindolinones, ambiguines, fischambiguines, fisherindoles, and welwitindolinones, which are only found in cyanobacteria of subsection V. Their structural diversity is due to the cyclisation, methylation, oxygenation and chlorination of terpene precursors [16]. Hapalindole isolated from *Fischerella* sp. has been found to possess antibacterial activity against gram negative and gram positive bacteria such as; *Escherichia coli* ATCC25992 and *Staphylococcus aureus* ATCC25923 [13].

#### **2.4. Isoprenoids**

A wide range of isoprenoids (also known as terpenoids) are produced by cyanobacteria, which have a common pathway utilising isoprene diphosphate (IDP) and dimethylallyl triphosphate (DMADP) precursors. These have many possible configurations resulting in high structural diversity due to modification by cyclisation, rearrangements and oxidation [17]. They are biosynthesized through the methylerythritol-phosphate (MEP) pathway. Using glyceraldehyde-3-phosphate and pyruvate produced from photosynthesis, the five carbon building blocks IPD and DMADP are formed [17].

The smallest group of isoprenoids is the hemiterpenes, which are formed from a single isoprene unit composed of five carbons. Monoterpenes have 10 carbons and are formed from IDP and DMADP or two molecules of DMADP monomers to form geranyl diphosphate (GDP). An example includes 2-methylisabomeol, which gives taste and odour to water. Geosmin (**Figure 1 (8)**) in an odorous sesquiterpene found in *Nostoc punctiforme* PCC 73102, which gives rise to its earthy smell and is synthesised from the condensation of an IDP molecule to the monoterpene GDP to form farnesyl diphosphate (FDP) [17, 18].

An abundant group of isoprenoids found in cyanobacteria are the carotenoids. These are tetraterpenes formed from the head to head condensation of two geranyl geranyl diphosphate (GGDP) molecules [17]. Located within cell membranes due to their hydrophobic nature, this group of metabolites can be divided into two classes; carotenes, hydrocarbon carotenoids such as β-carotene (**Figure 1 (9)**) and xanthophylls, which are oxygenated derivatives of hydrocarbon carotenoids such as zeaxanthin (**Figure 1 (10)**). Other carotenoids commonly found within cyanobacteria are echinenone, canthaxanthin and myxoxanthophyll. In many cases individual carotenoids could be considered as primary rather than secondary metabolites because of their role in photosynthesis however, other carotenoids are more specifically involved in photoprotection and in antioxidant protection and therefore fall into the secondary metabolites category [19].
