Genome mining for natural product biosynthetic gene clusters in the Subsection V cyanobacteria.
BACKGROUND
Cyanobacteria are well known for the production of a range of secondary metabolites. Whilst recent genome sequencing projects has led to an increase in the number of publically available cyanobacterial genomes, the secondary metabolite potential of many of these organisms remains elusive. Our study focused on the 11 publically available Subsection V cyanobacterial genomes, together with the draft genomes of Westiella intricata UH strain HT-29-1 and Hapalosiphon welwitschii UH strain IC-52-3, for their genetic potential to produce secondary metabolites. The Subsection V cyanobacterial genomes analysed in this study are reported to produce a diverse range of natural products, including the hapalindole-family of compounds, microcystin, hapalosin, mycosporine-like amino acids and hydrocarbons.


RESULTS
A putative gene cluster for the cyclic depsipeptide hapalosin, known to reverse P-glycoprotein multiple drug resistance, was identified within three Subsection V cyanobacterial genomes, including the producing cyanobacterium H. welwitschii UH strain IC-52-3. A number of orphan NRPS/PKS gene clusters and ribosomally-synthesised and post translationally-modified peptide gene clusters (including cyanobactin, microviridin and bacteriocin gene clusters) were identified. Furthermore, gene clusters encoding the biosynthesis of mycosporine-like amino acids, scytonemin, hydrocarbons and terpenes were also identified and compared.


CONCLUSIONS
Genome mining has revealed the diversity, abundance and complex nature of the secondary metabolite potential of the Subsection V cyanobacteria. This bioinformatic study has identified novel biosynthetic enzymes which have not been associated with gene clusters of known classes of natural products, suggesting that these cyanobacteria potentially produce structurally novel secondary metabolites.
School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia. m.micallef@uws.edu.au.
Melinda L
ML
Micallef
School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia. p.dagostino@unsw.edu.au.|School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, 2052, Australia. p.dagostino@unsw.edu.au.
Paul M
PM
D'Agostino
Department of Chemistry, Case Western Reserve University, 2740 Millis Science Center, Adelbert Road, Cleveland, OH, 44106, USA. dxs479@case.edu.
Deepti
D
Sharma
Department of Chemistry, Case Western Reserve University, 2740 Millis Science Center, Adelbert Road, Cleveland, OH, 44106, USA. rajesh.viswanathan@case.edu.
Rajesh
R
Viswanathan
School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia. m.moffitt@uws.edu.au.
Michelle C
MC
Moffitt
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D000458:Cyanobacteria / Q000235:genetics*; D016680:Genome, Bacterial; D006838:Hydrocarbons / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010453:Peptide Synthases / Q000378:metabolism; D064210:Secondary Metabolism / Q000235:genetics; D013729:Terpenes / Q000378:metabolism
D001426:Bacterial Proteins; D001688:Biological Products; D006838:Hydrocarbons; D013729:Terpenes; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase