Identification of Cryptic Products of the Gliotoxin Gene Cluster using NMR-based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis
| Autor: | Barbara J. Howlett, Nancy P. Keller, Ellen M. Fox, Frank C. Schroeder, DaWoon Chung, Ry R. Forseth |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Magnetic Resonance Spectroscopy
Virulence Peptide Human pathogen medicine.disease_cause Biochemistry Catalysis Article Aspergillus fumigatus chemistry.chemical_compound Colloid and Surface Chemistry Metabolomics Gliotoxin parasitic diseases Gene cluster medicine skin and connective tissue diseases chemistry.chemical_classification Mutation biology Chemistry General Chemistry biology.organism_classification Multigene Family |
| Popis: | Gliotoxin (1), a major product of the gli non-ribosomal peptide synthetase (NRPS) gene cluster, is strongly associated with virulence of the opportunistic human pathogen Aspergillus fumigatus. Despite identification of the gli cluster, the pathway of gliotoxin biosynthesis has remained elusive, in part because few potential intermediates have been identified. In addition, previous studies suggest that knowledge of gli-dependent metabolites is incomplete. Here we use differential analysis by 2D NMR spectroscopy (DANS) of metabolite extracts derived from gli knock-out and wild-type (WT) strains to obtain a detailed inventory of gli-dependent metabolites. DANS-based comparison of the WT metabolome with that of ΔgliZ, a knock-out strain devoid of the gene encoding the transcriptional regulator of the gli cluster, revealed nine novel gliZ-dependent metabolites including unexpected structural motifs. Their identification provides insight into gliotoxin biosynthesis and may benefit studies of the role of the gli cluster in A. fumigatus virulence. Our study demonstrates the utility of DANS for correlating gene expression and metabolite biosynthesis in microorganisms. |
| Databáze: | OpenAIRE |
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