title: The non-ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom-forming cyanobacterium Nodularia spumigena.
abstract: Nodularia spumigena is a filamentous nitrogen-fixing cyanobacterium that forms toxic blooms in brackish water bodies worldwide. Spumigins are serine protease inhibitors reported from a single strain of N. spumigena isolated from the Baltic Sea. These linear tetrapeptides contain non-proteinogenic amino acids including a C-terminal alcohol derivative of arginine. However, very little is known about these compounds despite the ecological importance of N. spumigena. We show that spumigins are assembled by two non-ribosomal peptide synthetases encoded in a 21 kb biosynthetic gene cluster. The compact non-ribosomal peptide synthetase features a reductive loading and release mechanism. Our analyses demonstrate that the bulk of spumigins produced by N. spumigena are released as peptide aldehydes in contrast to earlier findings. The main spumigin E variant contains an argininal residue and is a potent trypsin inhibitor. Spumigins were present in all of the N. spumigena strains isolated from the Baltic Sea and comprised up to 1% of the dry weight of the cyanobacterium. Our results demonstrate that bloom-forming N. spumigena strains produce a cocktail of enzyme inhibitors, which may explain in part the ecological success of this cyanobacterium in brackish water bodies worldwide.
authors.affiliation: Department of Applied Chemistry and Microbiology, University of Helsinki, Viikki Biocenter, Viikinkaari, Finland.
authors.forename: David P
authors.initials: DP
authors.lastname: Fewer
authors.forename: Jouni
authors.initials: J
authors.lastname: Jokela
authors.forename: Leo
authors.initials: L
authors.lastname: Rouhiainen
authors.forename: Matti
authors.initials: M
authors.lastname: Wahlsten
authors.forename: Kerttu
authors.initials: K
authors.lastname: Koskenniemi
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Stal
authors.forename: Kaarina
authors.initials: K
authors.lastname: Sivonen
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000737:chemistry; D002853:Chromatography, Liquid; D023061:Gene Order; D005798:Genes, Bacterial; D013058:Mass Spectrometry; D015394:Molecular Structure; D005810:Multigene Family; D046932:Nodularia / Q000302:isolation & purification / Q000378:metabolism*; D009842:Oligopeptides / Q000096:biosynthesis* / Q000737:chemistry; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000378:metabolism; D010802:Phylogeny; D012623:Seawater / Q000382:microbiology; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase