**4. Activity profiling of extracts**

An alternative technique to the time-consuming and expensive methods previously used for creating extensive collections of isolated and structurally characterized natural products [29] is screening the mixtures of compounds obtained from extracts of cyanobacteria strains [11]. Yet, obtaining extracts with potential biologically active novel compounds is not always simple from primary screenings. This probability can be predicted by comparing the ratio of the binding potencies at two receptor sites for a known selective ligand and for an extract by the "differential smart screens" method [30]. Furthermore, by means of a database of the usefulness of an extensive variety of identified bioactive compounds the analysis of drugs with the unknown process is imaginable. Therefore, information about previously unidentified compounds can be gained, which is precious for the antibiotic applications stated below [31]:


These techniques could lead to a novel understanding of the potential effects of untested compounds (or exposure to compounds not structurally analogous and, thus, not expected to act via the same biological target) [2].

Bioinformatics and proteomics experiments are used in studies at the mRNA (transcriptome) or protein (proteome) levels, which help with the identification *Cyanobacteria Natural Products as Sources for Future Directions in* Antibiotic *Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.106364*

of DNA binding sites of transcription factors [32] and the adjustment of biological functions, respectively, in order to characterize the complex organism responses to environmental stimulates [2]. Microarrays have been used for the identification of regulon members and stimulons by many groups in the transcriptome measurement level [33, 34].

Two-dimensional gel electrophoresis in which proteins are separated according to their molecular weight and isoelectric point, is useful in most cases, but intricate protein samples can also be analyzed using the liquid chromatography-tandem MS (LC-MS/MS) in which protein and peptide combinations are supplied to a mass spectrometer (MS) from a HPLC system. Isotopic dilution strategies on a MS instrument (e.g., isotope-coded affinity tags or ICAT) can be used for a comparative quantification of protein expression. ICAT approaches were advantageous when first released but are limited by their inability to analyze more than two conditions without a large amount of multiplexing [2, 35]. Currently, a developed version of the iTRAQ approach can analyze eight different conditions simultaneously. Despite all these tools, the most useful method would involve a concurrent quantification of the expression of all the genes and proteins of interest from a biological sample.

### **5. Natural products as pharmacological instruments**

Aside from their curative activity, natural bioactive products can operate as pharmacological instruments demonstrating novel physiological features [14]. Cyanobacteria are stubbornly obstinate to genetic manipulation, which is accessible only for a small number of strains [3]. The modularity in cyanobacterial PKS-NRPS gene clusters authorizes the heterologous expression of natural bioactive products and, thus, genetic manipulation for combinatorial biosynthesis of innovative hybrid chemical bioactive products [4]. The prosperous production of nonribosomal and ribosomal peptides in heterologous hosts permits the usage of other cyanobacterial natural bioactive products [3]. Cyanobacteria usually synthesize multiple variants of the identical natural bioactive product; this can be ascribed to a deficiency of the inactivity of the NRPS tailoring enzymes or NRPS biosynthetic pathways. The genetic basis for this modification of secondary metabolite gene clusters is probably controlled by gene duplications, gene deletions, recombination, sequential mutation followed by natural selection, and loss and gain of tailoring enzymes [36]. However, the evolutionary and adaptive importance of these processes is deficiently understood.

### **6. Which cyanobacteria phyla produce therapeutics?**

Throughout the prior decade, several natural bacterial compounds have been described, all of which originated from five bacterial phyla: Bacteroidetes (34 compounds), cyanobacteria (220), actinobacteria (256), proteobacteria (78), firmicutes (35), and four bioactive compounds from taxonomically unknown sources [37]. The variety of cyanobacterial natural bioactive products gathers > 1100 secondary compounds recognized with composite chemical structures, stated from different genera [3]. These metabolites represent a broad range of bioactivities including some that may be related to their natural environment (antibacterial, antifungal, antiviral, and cytotoxic) [29], but others demonstrate a clear pharmaceutical interest, for example, they can be used as anticancer agents, immunomodulators, or protease inhibitors [38]. Cyanobacteria exhibit different growth forms, from unicellular to filamentous or colonial forms, and depending on their environmental conditions they may be surrounded by a mucilaginous or gelatinous sheath [29]. The PKS and NRPS genes seem to be more widespread in undifferentiated filamentous and heterocystous cyanobacterial strains. Despite the current taxonomic instability within cyanobacteria, which makes assessing the actual occurrence of natural products difficult, cyanobacterial compounds are mainly obtained from the lyngbya, symploca, microcystis, nostac, and hapalosiphon (**Table 1**) [3, 37].



*Cyanobacteria Natural Products as Sources for Future Directions in* Antibiotic *Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.106364*

**Table 1.**

*Current status of potential cyanobacteria therapeutics.*
