title: Linking chemistry and genetics in the growing cyanobactin natural products family.
abstract: Ribosomal peptide natural products are ubiquitous, yet relatively few tools exist to predict structures and clone new pathways. Cyanobactin ribosomal peptides are found in ~30% of all cyanobacteria, but the connection between gene sequence and structure was not defined, limiting the rapid identification of new compounds and pathways. Here, we report discovery of four orphan cyanobactin gene clusters by genome mining and an additional pathway by targeted cloning, which represented a tyrosine O-prenylating biosynthetic pathway. Genome mining enabled discovery of five cyanobactins, including peptide natural products from Spirulina supplements. A phylogenetic model defined four cyanobactin genotypes, which explain the synthesis of multiple cyanobactin structural classes and help direct pathway cloning and structure prediction efforts. These strategies were applied to DNA isolated from a mixed cyanobacterial bloom containing cyanobactins.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Donia
authors.forename: Eric W
authors.initials: EW
authors.lastname: Schmidt
mesh_terms: D000595:Amino Acid Sequence; D001688:Biological Products / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D000458:Cyanobacteria / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D019587:Dietary Supplements / Q000382:microbiology; D016680:Genome, Bacterial / Q000235:genetics; D056186:Metagenomics; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D010455:Peptides / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D001688:Biological Products; D010455:Peptides; D012269:Ribosomal Proteins