Article

The non-ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom-forming cyanobacterium Nodularia spumigena.

Department of Applied Chemistry and Microbiology, University of Helsinki, Viikki Biocenter, Viikinkaari, Finland.
Molecular Microbiology (impact factor: 5.01). 09/2009; 73(5):924-37. DOI:10.1111/j.1365-2958.2009.06816.x pp.924-37
Source: PubMed

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.

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    Article: Insights into the Physiology and Ecology of the Brackish-Water-Adapted Cyanobacterium Nodularia spumigena CCY9414 Based on a Genome-Transcriptome Analysis
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    ABSTRACT: Nodularia spumigena is a filamentous diazotrophic cyanobacterium that dominates the annual late summer cyanobacterial blooms in the Baltic Sea. But N. spumigena also is common in brackish water bodies worldwide, suggesting special adaptation allowing it to thrive at moderate salinities. A draft genome analysis of N. spumigena sp. CCY9414 yielded a single scaffold of 5,462,271 nucleotides in length on which genes for 5,294 proteins were annotated. A subsequent strand-specific transcriptome analysis identified more than 6,000 putative transcriptional start sites (TSS). Orphan TSSs located in intergenic regions led us to predict 764 non-coding RNAs, among them 70 copies of a possible retrotransposon and several potential RNA regulators, some of which are also present in other N2-fixing cyanobacteria. Approximately 4% of the total coding capacity is devoted to the production of secondary metabolites, among them the potent hepatotoxin nodularin, the linear spumigin and the cyclic nodulapeptin. The transcriptional complexity associated with genes involved in nitrogen fixation and heterocyst differentiation is considerably smaller compared to other Nostocales. In contrast, sophisticated systems exist for the uptake and assimilation of iron and phosphorus compounds, for the synthesis of compatible solutes, and for the formation of gas vesicles, required for the active control of buoyancy. Hence, the annotation and interpretation of this sequence provides a vast array of clues into the genomic underpinnings of the physiology of this cyanobacterium and indicates in particular a competitive edge of N. spumigena in nutrient-limited brackish water ecosystems.
    PLoS ONE 01/2013; 8(3):e60224. · 4.09 Impact Factor

Keywords

21 kb biosynthetic gene cluster
 
argininal residue
 
Baltic Sea
 
bloom-forming N. spumigena strains
 
brackish water bodies
 
C-terminal alcohol derivative
 
compact non-ribosomal peptide synthetase features
 
dry weight
 
enzyme inhibitors
 
filamentous nitrogen-fixing cyanobacterium
 
forms toxic blooms
 
main spumigin E variant
 
N. spumigena
 
N. spumigena strains
 
Nodularia spumigena
 
non-proteinogenic amino acids
 
non-ribosomal peptide synthetases encoded
 
potent trypsin inhibitor
 
reductive loading
 
single strain