GREAT AT SMALL THINGS

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Are BCCM/ULC cyanobacteria bioactive against BCCM/IHEM fungi?

Lara Yannick1, Becker Pierre2 & A. Wilmotte3

 

1 InBios, Centre for Protein Engineering, B6a, University of Liège, 4000 Liège

2 BCCM/IHEM, Scientific Institute of Public Health, Section Mycology and Aerobiology, Rue J. Wytsmanstraat 14, 1050 Brussels

3 BCCM/ULC, Centre for Protein Engineering, B6a, University of Liège, 4000 Liège

 

An informal collaboration has been started between the BCCM/IHEM and BCCM/ULC collections to study the secondary metabolites that are produced by the cyanobacteria. ‘Secondary metabolites’ is a generic name qualifying peptides or compounds that are not essential for the life of the organism. The secondary metabolites are synthesized by the classical ribosomal pathway, by non-ribosomal peptide synthetase (NRPS), and/or polyketide synthetase (PKS) pathways. Until now, the ecological role of cyanobacterial secondary metabolites has not been solved. It may be useful for the organism against predation, for competition, fouling or resistance to extreme conditions.

Such molecules represent an increasing interest to the pharmaceutical industry (Singh et al., 2011). Indeed, they may have biological activities such as toxins (Moreira et al. 2013), antiviral, antibacterial, antiprotozoal, antifungal, or antitumoral (Niedermeyer, 2015). During the last two decades, most of the effort was devoted to the study of toxic properties of these molecules. These include neurotoxicity (anatoxin, saxitoxin), cytotoxicity (lyngbyatoxin), inflammatory agents and hepatotoxicity (aplysiatoxin,cylindrospermospin, LPS, microcystins, nodularins) (Codd et al., 2005; Sivonen and Börner, 2008; Pearson et al., 2010).

The active quest for the discovery of cyanobacterial metabolites gave rise to a considerable amount of listed compounds, which can be organized in five major groups of molecules (Van Wagoner et. al, 2007). The first group (i) consists of polyketides, which is a large and diverse group that comprise linear or cyclic polyketides (e.g. oscillatoxin, etc.). Polyketides have a structurally intriguing carbon skeleton that comprises polyethers, polyenes, polyphenols, macrolides and enediynes. They are produced by the superfamily of enzyme called PKS. The second group (ii) is represented by the cyanopeptides, a large and diverse group of molecules (e.g. cyanopeptolins, microcystins, microginins, microviridins etc.), which can also be divided in linear and cyclic peptides weighting 300 to 2000 Da. For now, studies on the biosynthesis pathway of cyanopeptides revealed that a NRPS complex, a hybrid NRPS-PKS complex, as well as a traditional ribosomal pathway (e.g. cyanobactins) could code for the biosynthesis of these peptides. The third group (iii) is represented by the alkaloids (e.g. anatoxin, BMAA, curacin, cylindrospermopsin, saxitoxin, scytonemin, etc.) which can be divided in two subgroups: the linear-like and the ring-like alkaloids. NRPS-PKS hybrids (Nunnery et al., 2010) and ribosomally expressed gene cluster (Soule et al., 2009) have been related to the biosynthesis of alkaloids. The fourth group includes the isoprenoids, which includes carotenoids and terpenoids. Finally, the fifth group gathers protein such as the potent anti-HIV molecule cyanovirin-N (Bolmstedt et al., 2001) and other aromatic compounds (Lara, 2014).

During the FP4 EC project MICROMAT coordinated by the promoter of BCCM/ULC and to which the host labs of BCCM/LMG and BCCM/DCG have participated, the bioactivities of a number of Antarctic strains against pathogenic bacteria and fungi have been demonstrated (Taton et al., 2006, Biondi et al., 2008). Subsequently, the studied strains were deposited in BCCM/ULC.      

In this context, partners of the BCCM consortium naturally collaborated to investigate the potential antimicrobial capabilities of the cyanobacteria preserved by BCCM/ULC. In particular, their extracts were tested on different fungal pathogens from the BCCM/IHEM collection. A first screening identifed a fraction that inhibited the growth of both yeasts and moulds. Characterization of the active molecule and toxicological studies are currently in progress. These analyses will determine if this molecule can be a candidate as a new antifungal drug. Further screening (additional extracts and pathogens) is also part of the project.

 

References

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