A Nonribosomal Peptide Synthetase-Derived Iron(III) Complex from the Pathogenic Fungus Aspergillus fumigatus

作者：Yin Wen Bing; Baccile Joshua A; Bok Jin Woo; Chen Yiming; Keller Nancy P^*; Schroeder Frank C

来源：Journal of the American Chemical Society, 2013, 135(6): 2064-2067.

DOI：10.1021/ja311145n

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 NAPS pathway producing the anticancer fumitremorgins.

• 出版日期2013-2-13