2011
DOI: 10.1073/pnas.1106399108
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Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus

Abstract: Aspergillus fumigatus is the most common airborne fungal pathogen for humans. In this mold, iron starvation induces production of the siderophore triacetylfusarinine C (TAFC). Here we demonstrate a link between TAFC and ergosterol biosynthetic pathways, which are both critical for virulence and treatment of fungal infections. Consistent with mevalonate being a limiting prerequisite for TAFC biosynthesis, we observed increased expression of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase (Hmg1) under iron starv… Show more

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Cited by 116 publications
(138 citation statements)
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“…The GC program and MS operation conditions were the same as those described previously (45,46). Sterol identification was based on interpretation and comparison of mass spectra and retention time data with previous data (45,47). The amount of each sterol (in micrograms) relative to the dry weight (in grams) of the fungus was calculated from three biological replicates analyzed in triplicate by GC-MS.…”
Section: Methodsmentioning
confidence: 99%
“…The GC program and MS operation conditions were the same as those described previously (45,46). Sterol identification was based on interpretation and comparison of mass spectra and retention time data with previous data (45,47). The amount of each sterol (in micrograms) relative to the dry weight (in grams) of the fungus was calculated from three biological replicates analyzed in triplicate by GC-MS.…”
Section: Methodsmentioning
confidence: 99%
“…In fungi acyl-CoA ligase SidI converts mevalonate to mevalonylCoA, and enoyl-CoA hydratase SidH transforms mevalonyl-CoA to anhydromevalonyl-CoA (33). We speculated that anhydromevalonyl-CoA could spontaneously cyclize into anhydromevalonolactone intracellularly.…”
Section: Construction Of a Nonnatural Metabolic Pathway For Biosynthementioning
confidence: 99%
“…Family 2 comprised one S. cerevisiae protein, Fat2p, one A. nidulans protein, FatD, and N. crassa ACS-7 (encoded by NCU08935). An A. fumigatus homolog of one of the ACS proteins within family 1 in A. nidulans (AN0609), termed SidI, localized to the peroxisome and was recently characterized as a mevalonyl-CoA ligase involved in siderophore (triacetylfusarinine C [TAFC]) biosynthesis (45,46). Two additional ACSs in family 1 (AN5272 and AN4659) were identified by in silico sequence analysis and are predicted to localize to the peroxisome (AN5272) or to mitochondria (AN4659); AN4659 was predicted to have short-chain FA specificity (21).…”
Section: Resultsmentioning
confidence: 99%