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A nonribosomal peptide synthetase-derived iron(III) complex from the pathogenic fungus Aspergillus fumigatus.

ABSTRACT: Small molecules (SMs) play central roles as virulence factors of pathogenic fungi and bacteria; however, genomic analyses suggest that the majority of microbial SMs have remained uncharacterized. Based on microarray analysis followed by comparative metabolomics of overexpression/knockout mutants, we identified a tryptophan-derived iron(III)-complex, hexadehydro-astechrome (HAS), as the major product of the cryptic has nonribosomal peptide synthetase (NRPS) gene cluster in the human pathogen Aspergillus fumigatus. Activation of the has cluster created a highly virulent A. fumigatus strain that increased mortality of infected mice. Comparative metabolomics of different mutant strains allowed to propose a pathway for HAS biosynthesis and further revealed cross-talk with another NRPS pathway producing the anticancer fumitremorgins.

SUBMITTER: Yin WB

PROVIDER: S-EPMC3590312 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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A nonribosomal peptide synthetase-derived iron(III) complex from the pathogenic fungus Aspergillus fumigatus.

Yin Wen-Bing WB Baccile Joshua A JA Bok Jin Woo JW Chen Yiming Y Keller Nancy P NP Schroeder Frank C FC

Journal of the American Chemical Society 20130201 6

Small molecules (SMs) play central roles as virulence factors of pathogenic fungi and bacteria; however, genomic analyses suggest that the majority of microbial SMs have remained uncharacterized. Based on microarray analysis followed by comparative metabolomics of overexpression/knockout mutants, we identified a tryptophan-derived iron(III)-complex, hexadehydro-astechrome (HAS), as the major product of the cryptic has nonribosomal peptide synthetase (NRPS) gene cluster in the human pathogen Aspe ...[more]

PMID: 23360537

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