Protein: Nonribosomal peptide synthetase sidD (NPRS sidD) (EC 6.3.2.-) (Siderophore synthetase D) (Q4WF53)
Organism: Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293) (Neosartorya fumigata)
Function: Nonribosomal peptide synthase; part of the siderophore biosynthetic pathway. 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. Subsequently, the pathways for biosynthesis of extra- and intracellular siderophores split. For biosynthesis of extracellular siderophores, the transacylase sidF transfers anhydromevalonyl to N(5)-hydroxyornithine. The required anhydromevalonyl-CoA moiety is derived from mevalonate by CoA ligation and dehydration catalyzed by sidI and sidH respectively. The acetylation of N(5)-hydroxyornithine for FC biosynthesis involves the constitutively expressed sidL. FC is hydroxylated to HFC by an as yet uncharacterized enzyme during conidiation. Assembly of fusarinine C (FsC) and FC is catalyzed by two different nonribosomal peptide synthetases (NRPS), sidD and sidC respectively. Subsequently, sidG catalyzes N2-acetylation of FsC for forming TAFC. Both extra- and intracellular siderophores are crucial for growth during iron limitation and virulence.
Sequence: MGSIQQDDVHNQIDHCNQSDDLPAARLNCNDVELFEVAGLACDETSSPTGMRDEMVLLSWLIALLRTREGGQIRYEWAYRYPEEEPVPRCLAMNEVVAGLQSSVKETAAAVSRHISADVSSPPAPASLLLSTSSLSQTSDEAKDEGLLHLEIAFENGLCKIRPTWHSENMLPFTVTRYARTLIDTVRLCISNCDAAIQDCLRPTAYDLDEIWRWNHNLPPTYNFCMHEIISDQAQKFPDKEAIASWDGSLTYRQIDQYSSFVARSLIGMGVGLHDVLPVCFEKSRWTIVAVLAVMKAGATFVLMDPTLPLARLQNMAQQVGAKMMVSSRGQYNLATEIIPNANVLVVEENTFSSLSAEQNGEPLPTVPSSALMYMIFTSGSTGTPKGVKISHETYTSSAIPRANAVGYTEDSRVLDFASYAFDVSIDSMLLTLGNGGCLCIPSDEDRLNDINGVIRRMKVNYAGLTPSVARILDADVISSLSGLGLGGEAVSARDVNLWGQDTRIIIGYGPCECTIGCTVNSSAATGRDYISIGPGNGAVIWIVDPNDHESLVPLGAVGELLVEGPIVGQGYLNDPEKTAAAFIEDPSWLVAGHEGYPGRRGRLYKTGDLGRYDPDGSGGIVFVGRKDTQVKLRGQRVELGEIESQLRARLPSETTVIAEVIVPQGSGGQPTLVAFVAAQTTKGHDHTGLEAAELPDELRRALSEADAELAKVLPRYMVPTAYIPVNHIPTLISGKTDRKRLRQFGATVDLRQLDQDATNTAARELSDLERRLRQAWSQTLKLQACSIRLQDNFFALGGDSLTAMKLVSVCRSQGLDLSVTSMFSNPTLSAMASVVRICDVDVQRTVPAFSMITSDMNSACVEAAEPCGVGPADIEDIYPCTPTQESLFTFSLKSVKPYVAQRVLCIPSHIDLNAWRKAWEDVVAALPILRTRVAQLQEPGLQQVVLKNSISWTQASDLAEYLENDRTQKMNLGESLARYAIVEDSADGKRYMVWTIHHVLYDGWSEPIILKQVSDALQGQPVEVKAQMRDFVRFVRDSDDAAVQEFWRRELKGAVGPQFPRLPSRDFMPTPDALVERQVSLDTSSGSPFTMATLIRGAWALVASQYTGSDDIVFGETLTGRDIPLPGVESIVGPLIATVPIRVRILRGSTVESYLQAVQQSVLARTPYQHLGMQNIRKVSQDAQHACETGTGLVIQPEPEYVGSELGVERGDVVLEALHFNPYPLMLACGIRKGGFRVCASFDSSLIETRQMERMLAQLETACWQLSQGLSRKVDEISCLPEAELNQIWQWNRSPPLSLDETTSRLRANASTKPGSSYPPAVVPWVCSPRNSSLLSPIGCVGELWLEGALLSGDTVDSPAWLVAGSSTCAGRTGKVQATGDMVQLREDGSLVFVGRKENVVPVQGHAVDITEIERHLAEHLPPTIRAAATVVRSSSDQELVMFIEQPAAEEACIELLSEKREIVCDAPDKAFQTTICATIPGSLAAVLKKLDKYMRDSLPSYMAPSAYIVVEKLPNTMDDIDHNLLNQIASQVTPQILNELRDGLSNAWTKATAPNHLSASESILRSAWAKVLRVDPEQIDVDDNFFRRGGDSVLAMKLVSSLRAQGYSLSVADIFRHMRLSDAARVMKVDERSTEKINSYQPFSMLRLPDVQQFLANIVRPQLGDQHWPIRDVLPVTDSQDMDIRATIQPPRTSIQYTMLYFDNSVDRERLFRSCSDLVKTHEILRTVFISHESSFLQVVLNELEIPVRAHKTDKQLDQYVASLFREDIESNFQLGCPFLRLFYVEGNNGESCLVIGLSHAQYDGVSLPRLLQDLDALYTGTQLATFSPFSLYMAQTSEEAIQNKAAAYWRNLLSSSSLSTLDGPSSDPTDKAIFHTRPVNIHPLKEITTANLLTAAWAMVLARRLQTPDVTFGSVTSGRTLDIPNAENFMGPCYQLTPVRVPFHPDWTASDLLNFVQTQSAESAAHDFLGFEKIAKLAGWASGRQGFDSIVHHQDWEDFDMMPFGGGSCRVDIANPHGDAAYPVKAVSFVKEGEIHVGVVCSERDVMFVDEVLGELAAAVVELAGQSTEVLLDSKLFSGQ
InterPro domains: - IPR042099: ANL, N-terminal domain (homologous_superfamily) [207-627]
- IPR020806: Polyketide synthase-like, phosphopantetheine-binding domain (domain) [770-1623]
- IPR000873: AMP-dependent synthetase/ligase domain (domain) [232-573]
- IPR036736: ACP-like superfamily (homologous_superfamily) [764-1629]
- IPR045851: AMP-binding enzyme, C-terminal domain superfamily (homologous_superfamily) [628-1548]
- IPR023213: Chloramphenicol acetyltransferase-like domain superfamily (homologous_superfamily) [873-1829]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [764-1633]
- IPR020845: AMP-binding, conserved site (conserved_site) [375-386]
- IPR010071: Amino acid adenylation domain (domain) [251-652]
- IPR001242: Condensation domain (domain) [876-1997]
- IPR056896: Nonribosomal peptide synthetase sidD, N-terminal (domain) [32-201]
Interaction partners: - N
- 4'-phosphopantetheinyl transferase A
- Mevalonyl-coenzyme A hydratase sidH
- FsC-acetyl coenzyme A-N
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016874 (ligase activity), GO:0016879 (ligase activity, forming carbon-nitrogen bonds), GO:0016881 (acid-amino acid ligase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043603 (amide metabolic process), GO:0006790 (sulfur compound metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0006518 (peptide metabolic process), GO:0044272 (sulfur compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0043604 (amide biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0043043 (peptide biosynthetic process), GO:0043386 (mycotoxin biosynthetic process), GO:0019184 (nonribosomal peptide biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0031982 (vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0097708 (intracellular vesicle)