Cyanobactins and anticancer bioactivity of cyanobacterial extracts

Cyanobacteria have been found to be a prolific source of novel bioactive natural products. Among those, recent studies have put the focus on a group of small ribosomal cyclic peptides, the cyanobactins. Their reported bioactivities (including anticancer) have made this group of compounds potential as pharmaceutical leads. Apart from cyanobactins, other anticancer compounds have been isolated from cyanobacteria. Our laboratory maintains a cyanobacterial culture collection (LEGE CC) of >350 isolates from diverse environments, representing an untapped resource of biological and chemical diversity. We have started a screening program using LEGE CC isolates in order to (1) detect the presence of genes involved in cyanobactin biosynthesis and study the phylogenetic relationship among strains; and (2) obtain crude extracts and test their ability to inhibit the anticancer targets: 20S proteasome and histone deacetylase (HDAC). Heretofore, cyanobactin related genes were found in strains belonging to three cyanobacterial orders (Oscillatoriales, Chroococcales and Nostocales). The phylogenetic analysis performed seems to reveal an uncovered diversity of these peptides since several cyanobactin gene sequences from LEGE CC strains are phylogenetically distant to the ones currently known cyanobactins. Moreover, cyanobacterial crude extracts exhibited 20S proteasome and HDAC inhibition activities, underscoring the potential for further discoveries of new natural products.