Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis
AuthorForseth, RR; Fox, EM; Chung, D; Howlett, BJ; Keller, NP; Schroeder, FC
Source TitleJOURNAL OF THE AMERICAN CHEMICAL SOCIETY
PublisherAMER CHEMICAL SOC
Document TypeJournal Article
CitationsForseth, RR; Fox, EM; Chung, D; Howlett, BJ; Keller, NP; Schroeder, FC, Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (25), pp. 9678 - 9681
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151163
C1 - Journal Articles Refereed
Gliotoxin, a major product of the gli non-ribosomal peptide synthetase 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.
KeywordsGenomics; Infectious Diseases
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