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

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• 作者：Wen-Bing Yin ; Joshua A. Baccile ; Jin Woo Bok ; Yiming Chen ; Nancy P. Keller ; Frank C. Schroeder
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：February 13, 2013
• 年：2013
• 卷：135
• 期：6
• 页码：2064-2067
• 全文大小：328K
• 年卷期：v.135,no.6(February 13, 2013)
• ISSN：1520-5126

文摘

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.