title: Analysis of an inactive cyanobactin biosynthetic gene cluster leads to discovery of new natural products from strains of the genus Microcystis.
abstract: Cyanobactins are cyclic peptides assembled through the cleavage and modification of short precursor proteins. An inactive cyanobactin gene cluster has been described from the genome Microcystis aeruginosa NIES843. Here we report the discovery of active counterparts in strains of the genus Microcystis guided by this silent cyanobactin gene cluster. The end products of the gene clusters were structurally diverse cyclic peptides, which we named piricyclamides. Some of the piricyclamides consisted solely of proteinogenic amino acids while others contained disulfide bridges and some were prenylated or geranylated. The piricyclamide gene clusters encoded between 1 and 4 precursor genes. They encoded highly diverse core peptides ranging in length from 7-17 amino acids with just a single conserved amino acid. Heterologous expression of the pir gene cluster from Microcystis aeruginosa PCC7005 in Escherichia coli confirmed that this gene cluster is responsible for the biosynthesis of piricyclamides. Chemical analysis demonstrated that Microcystis strains could produce an array of piricyclamides some of which are geranylated or prenylated. The genetic diversity of piricyclamides in a bloom sample was explored and 19 different piricyclamide precursor genes were found. This study provides evidence for a stunning array of piricyclamides in Microcystis, a worldwide occurring bloom forming cyanobacteria.
authors.affiliation: Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Leikoski
authors.forename: David P
authors.initials: DP
authors.lastname: Fewer
authors.forename: Jouni
authors.initials: J
authors.lastname: Jokela
authors.forename: Pirita
authors.initials: P
authors.lastname: Alakoski
authors.forename: Matti
authors.initials: M
authors.lastname: Wahlsten
authors.forename: Kaarina
authors.initials: K
authors.lastname: Sivonen
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D004220:Disulfides / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D014644:Genetic Variation; D046931:Microcystis / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics*; D010802:Phylogeny; D012270:Ribosomes / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D004220:Disulfides; D010456:Peptides, Cyclic