7oeq

Structural highlights

Function

SIDH_ASPFU Mevalonyl-coenzyme A hydratase; part of the siderophore biosynthetic pathway (PubMed:22106303). Aspergillus fumigatus produces 4 types of siderophores, low-molecular-mass iron chelators, including excreted fusarinine C (FsC) and triacetylfusarinine C (TAFC) for iron uptake and intacellular ferricrocin (FC) for hyphal and hydroxyferricrocin (HFC) for conidial iron distribution and storage. TAFC consists of 3 N(2)-acetyl-N(5)-anhydromevalonyl-N(5)-hydroxyornithine residues cyclically linked by ester bonds; FC is a cyclic hexapeptide with the structure Gly-Ser-Gly-(N(5)-acetyl-N(5)-hydroxyornithine)x3. The biosynthesis of all four siderophores depends on the hydroxylation of ornithine, catalyzed by the monooxygenase sidA (PubMed:15504822, PubMed:16113265). Subsequently, the pathways for biosynthesis of extra- and intracellular siderophores split (PubMed:17845073). For biosynthesis of extracellular siderophores, the transacylase sidF transfers anhydromevalonyl to N(5)-hydroxyornithine (PubMed:17845073). The required anhydromevalonyl-CoA moiety is derived from mevalonate by CoA ligation and dehydration catalyzed by sidI and sidH respectively (PubMed:22106303). The acetylation of N(5)-hydroxyornithine for FC biosynthesis involves the constitutively expressed sidL (PubMed:21622789). FC is hydroxylated to HFC by an as yet uncharacterized enzyme during conidiation (PubMed:17845073). Assembly of fusarinine C (FsC) and FC is catalyzed by two different nonribosomal peptide synthetases (NRPS), sidD and sidC respectively (PubMed:17845073). Subsequently, sidG catalyzes N2-acetylation of FsC for forming TAFC (PubMed:17845073). Both extra- and intracellular siderophores are crucial for growth during iron limitation and virulence (PubMed:16113265).^{[1] [2] [3] [4] [5]}

References

1. ↑ Schrettl M, Bignell E, Kragl C, Joechl C, Rogers T, Arst HN Jr, Haynes K, Haas H. Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med. 2004 Nov 1;200(9):1213-9. Epub 2004 Oct 25. PMID:15504822 doi:http://dx.doi.org/jem.20041242
2. ↑ Hissen AH, Wan AN, Warwas ML, Pinto LJ, Moore MM. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect Immun. 2005 Sep;73(9):5493-503. PMID:16113265 doi:http://dx.doi.org/10.1128/IAI.73.9.5493-5503.2005
3. ↑ Schrettl M, Bignell E, Kragl C, Sabiha Y, Loss O, Eisendle M, Wallner A, Arst HN Jr, Haynes K, Haas H. Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog. 2007 Sep 28;3(9):1195-207. doi: 10.1371/journal.ppat.0030128. PMID:17845073 doi:http://dx.doi.org/10.1371/journal.ppat.0030128
4. ↑ Blatzer M, Schrettl M, Sarg B, Lindner HH, Pfaller K, Haas H. SidL, an Aspergillus fumigatus transacetylase involved in biosynthesis of the siderophores ferricrocin and hydroxyferricrocin. Appl Environ Microbiol. 2011 Jul;77(14):4959-66. doi: 10.1128/AEM.00182-11. Epub , 2011 May 27. PMID:21622789 doi:http://dx.doi.org/10.1128/AEM.00182-11
5. ↑ Yasmin S, Alcazar-Fuoli L, Grundlinger M, Puempel T, Cairns T, Blatzer M, Lopez JF, Grimalt JO, Bignell E, Haas H. Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):E497-504. doi: , 10.1073/pnas.1106399108. Epub 2011 Nov 21. PMID:22106303 doi:http://dx.doi.org/10.1073/pnas.1106399108