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

### **2.1. Nonribosomal peptides and polyketides**

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

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

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

#### **2.2. Ribosomal peptides**

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], formally known as ribosomally synthesised and posttranslationally modified peptides (RiPP). Examples include the cyclic peptides patellamides, such as patellamide A (**Figure 1 (4)**) and the linear peptide aeruginosamide (**Figure 1 (5)**) [9].
