E9QYP0Q4X250Q5SE95SIDA_ASPFUL-ornithine N(5)-monooxygenaseOMO1.14.13.196L-ornithine N(5)-oxygenaseSiderophore biosynthesis protein AsidAAfu2g07680Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293)Neosartorya fumigataEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaeAspergillusAspergillus subgen. FumigatiSiderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence.NUCLEOTIDE SEQUENCE [GENOMIC DNA]FUNCTIONPATHWAYDISRUPTION PHENOTYPEThe Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N(5)-oxygenase, is required for virulence.NUCLEOTIDE SEQUENCE [GENOMIC DNA]FUNCTIONDISRUPTION PHENOTYPEGenomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection.FUNCTIONDISRUPTION PHENOTYPESreA-mediated iron regulation in Aspergillus fumigatus.INDUCTIONAspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor.FUNCTIONCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESCOFACTORPATHWAYSUBUNITMASS SPECTROMETRYComprehensive spectroscopic, steady state, and transient kinetic studies of a representative siderophore-associated flavin monooxygenase.FUNCTIONCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESCOFACTORSidL, an Aspergillus fumigatus transacetylase involved in biosynthesis of the siderophores ferricrocin and hydroxyferricrocin.FUNCTIONDual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase.FUNCTIONMevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus.FUNCTIONStructural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases.X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH FAD; NADP; L-ORNITHINE; LYSINE AND L-ARGININEL-ornithine N(5)-monooxygenase; part of the siderophore biosynthetic pathway (PubMed:15504822, PubMed:16113265, PubMed:17845073, PubMed:20614882, PubMed:20650894, PubMed:22465572). Aspergillus fumigatus produces four 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 three 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, PubMed:20614882, PubMed:20650894, PubMed:22465572). SidA is highly specific for its substrate, only hydrolyzing l-ornithine, and has preference for NADPH over NADH, NADPH playing a role in stabilization of the C4a-hydroperoxyflavin intermediate (PubMed:20614882, PubMed:22465572). 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).L-ornithine + NADPH + O2 = H2O + N(5)-hydroxy-L-ornithine + NADP(+)L-ornithine + NADH + O2 = H2O + N(5)-hydroxy-L-ornithine + NAD(+)FADBinds 1 FAD per subunit.1.7 mM for L-ornithine (in the presence of 1 mM NADH)1.7 mM for L-ornithine (in the presence of 1 mM NADPH)0.49 mM for L-ornithine (at 37 degrees Celsius)0.58 mM for L-ornithine (at 25 degrees Celsius)0.94 mM for NADPH (in the presence of 15 mM L-ornithine)0.9 mM for NADH (in the presence of 15 mM L-ornithine)4.6 uM for NADPH (at 37 degrees Celsius)2.6 uM for NADPH (at 25 degrees Celsius)18 uM for O(2) (at 37 degrees Celsius)16 uM for O(2) (at 25 degrees Celsius)kcat is 29 min(-1) with L-ornithine as substrate and 75 min(-1) with NADPH as substrate.Siderophore biosynthesis; ferrichrome biosynthesis.Homotetramer.Moderately reduced growth rate during iron starvation and in iron replete conditions. Only displays 1% of wild-type conidiospore production in iron-depleted and replete conditions. Completely attenuates virulence in a mouse model of invasive pulmonary aspergillosis.Belongs to the lysine N(6)-hydroxylase/L-ornithine N(5)-oxygenase family.3D-structureFADFlavoproteinMonooxygenaseNADPNucleotide-bindingOxidoreductaseReference proteomeFADFADsubstrateFADNADP(+)NADP(+)substrateNADP(+)substrateFADsubstrateMESVERKSESSYLGMRNMQPEQRLSLDPPRLRSTPQDELHDLLCVGFGPASLAIAIALHDALDPRLNKSASNIHAQPKICFLERQKQFAWHSGMLVPGSKMQISFIKDLATLRDPRSSFTFLNYLHQKGRLIHFTNLSTFLPARLEFEDYMRWCAQQFSDVVAYGEEVVEVIPGKSDPSSSVVDFFTVRSRNVETGEISARRTRKVVIAIGGTAKMPSGLPQDPRIIHSSKYCTTLPALLKDKSKPYNIAVLGSGQSAAEIFHDLQKRYPNSRTTLIMRDSAMRPSDDSPFVNEIFNPERVDKFYSQSAAERQRSLLADKATNYSVVRLELIEEIYNDMYLQRVKNPDETQWQHRILPERKITRVEHHGPQSRMRIHLKSSKPESEGAANDVKETLEVDALMVATGYNRNAHERLLSKVQHLRPTGQDQWKPHRDYRVEMDPSKVSSEAGIWLQGCNERTHGLSDSLLSVLAVRGGEMVQSIFGEQLERAAVQGHQLRAML
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License