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Functional Genomics of Novel Secondary Metabolites from Diverse Cyanobacteria Using Untargeted Metabolomics
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd, MS977R0181A, Berkeley, CA 94720, USA
DOE Joint Genome Institute, Walnut Creek, CA 94598, USA
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA
Institute Pasteur, Collection of Cyanobacteria, Paris Cedex 15 75724, France
* Author to whom correspondence should be addressed.
Received: 15 August 2013; in revised form: 21 August 2013 / Accepted: 9 September 2013 / Published: 30 September 2013
Abstract: Mass spectrometry-based metabolomics has become a powerful tool for the detection of metabolites in complex biological systems and for the identification of novel metabolites. We previously identified a number of unexpected metabolites in the cyanobacterium Synechococcus sp. PCC 7002, such as histidine betaine, its derivatives and several unusual oligosaccharides. To test for the presence of these compounds and to assess the diversity of small polar metabolites in other cyanobacteria, we profiled cell extracts of nine strains representing much of the morphological and evolutionary diversification of this phylum. Spectral features in raw metabolite profiles obtained by normal phase liquid chromatography coupled to mass spectrometry (MS) were manually curated so that chemical formulae of metabolites could be assigned. For putative identification, retention times and MS/MS spectra were cross-referenced with those of standards or available sprectral library records. Overall, we detected 264 distinct metabolites. These included indeed different betaines, oligosaccharides as well as additional unidentified metabolites with chemical formulae not present in databases of metabolism. Some of these metabolites were detected only in a single strain, but some were present in more than one. Genomic interrogation of the strains revealed that generally, presence of a given metabolite corresponded well with the presence of its biosynthetic genes, if known. Our results show the potential of combining metabolite profiling and genomics for the identification of novel biosynthetic genes.
Keywords: cyanobacteria; metabolomics; mass spectrometry; MS/MS; betaines; oligosaccharides
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Baran, R.; Ivanova, N.N.; Jose, N.; Garcia-Pichel, F.; Kyrpides, N.C.; Gugger, M.; Northen, T.R. Functional Genomics of Novel Secondary Metabolites from Diverse Cyanobacteria Using Untargeted Metabolomics. Mar. Drugs 2013, 11, 3617-3631.
Baran R, Ivanova NN, Jose N, Garcia-Pichel F, Kyrpides NC, Gugger M, Northen TR. Functional Genomics of Novel Secondary Metabolites from Diverse Cyanobacteria Using Untargeted Metabolomics. Marine Drugs. 2013; 11(10):3617-3631.
Baran, Richard; Ivanova, Natalia N.; Jose, Nick; Garcia-Pichel, Ferran; Kyrpides, Nikos C.; Gugger, Muriel; Northen, Trent R. 2013. "Functional Genomics of Novel Secondary Metabolites from Diverse Cyanobacteria Using Untargeted Metabolomics." Mar. Drugs 11, no. 10: 3617-3631.