A nonribosomal peptide synthetase-derived iron(III) complex from the pathogenic fungus Aspergillus fumigatus.
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.
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Wisconsin 53706, USA.
Wen-Bing
WB
Yin
Joshua A
JA
Baccile
Jin Woo
JW
Bok
Yiming
Y
Chen
Nancy P
NP
Keller
Frank C
FC
Schroeder
D001232:Aspergillus fumigatus / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005290:Ferric Compounds; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase