MS/MS networking guided analysis of molecule and gene cluster families.

TitleMS/MS networking guided analysis of molecule and gene cluster families.
Publication TypeJournal Article
Year of Publication2013
AuthorsNguyen D D, Wu C-H, Moree WJ, Lamsa A, Medema MH, Zhao X, Gavilan RG, Aparicio M, Atencio L, Jackson C, Ballesteros J, Sanchez J, Watrous JD, Phelan VV, van de Wiel C, Kersten RD, Mehnaz S, De Mot R, Shank EA, Charusanti P, Nagarajan H, Duggan BM, Moore BS, Bandeira N, Palsson BØ, Pogliano K, Gutiérrez M, Dorrestein PC
JournalProc Natl Acad Sci U S A
Volume110
Issue28
PaginationE2611-20
Date Published2013 Jul 9
ISSN1091-6490
KeywordsAmino Acid Sequence, Bacillus, Bacterial Proteins, Molecular Sequence Data, Multigene Family, Peptides, Pseudomonas, Tandem Mass Spectrometry
Abstract

The ability to correlate the production of specialized metabolites to the genetic capacity of the organism that produces such molecules has become an invaluable tool in aiding the discovery of biotechnologically applicable molecules. Here, we accomplish this task by matching molecular families with gene cluster families, making these correlations to 60 microbes at one time instead of connecting one molecule to one organism at a time, such as how it is traditionally done. We can correlate these families through the use of nanospray desorption electrospray ionization MS/MS, an ambient pressure MS technique, in conjunction with MS/MS networking and peptidogenomics. We matched the molecular families of peptide natural products produced by 42 bacilli and 18 pseudomonads through the generation of amino acid sequence tags from MS/MS data of specific clusters found in the MS/MS network. These sequence tags were then linked to biosynthetic gene clusters in publicly accessible genomes, providing us with the ability to link particular molecules with the genes that produced them. As an example of its use, this approach was applied to two unsequenced Pseudoalteromonas species, leading to the discovery of the gene cluster for a molecular family, the bromoalterochromides, in the previously sequenced strain P. piscicida JCM 20779(T). The approach itself is not limited to 60 related strains, because spectral networking can be readily adopted to look at molecular family-gene cluster families of hundreds or more diverse organisms in one single MS/MS network.

DOI10.1073/pnas.1303471110
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/23798442?dopt=Abstract
PMCPMC3710860
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID23798442