APDB_EMENI
ID APDB_EMENI Reviewed; 498 AA.
AC Q5ATH2; C8VEA9;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Cytochrome P450 monooxygenase apdB {ECO:0000303|PubMed:17369821};
DE EC=1.-.-.- {ECO:0000269|Ref.5};
DE AltName: Full=Aspyridones biosynthesis protein B {ECO:0000303|PubMed:17369821};
GN Name=apdB {ECO:0000303|PubMed:17369821}; ORFNames=AN8408;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=17369821; DOI=10.1038/nchembio869;
RA Bergmann S., Schuemann J., Scherlach K., Lange C., Brakhage A.A.,
RA Hertweck C.;
RT "Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus
RT nidulans.";
RL Nat. Chem. Biol. 3:213-217(2007).
RN [4]
RP FUNCTION.
RX PubMed=20828130; DOI=10.1021/ja107084d;
RA Xu W., Cai X., Jung M.E., Tang Y.;
RT "Analysis of intact and dissected fungal polyketide synthase-nonribosomal
RT peptide synthetase in vitro and in Saccharomyces cerevisiae.";
RL J. Am. Chem. Soc. 132:13604-13607(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX DOI=10.1039/c3sc51785c;
RA Wasil Z., Pahirulzaman K.A.K., Butts C., Simpson T.J., Lazarus C.M.,
RA Cox R.J.;
RT "One pathway, many compounds: Heterologous expression of a fungal
RT biosynthetic pathway reveals its intrinsic potential for diversity.";
RL Chem. Sci. 4:3845-3856(2013).
RN [6]
RP FUNCTION.
RX PubMed=25494235; DOI=10.1021/ol503179v;
RA Zou Y., Xu W., Tsunematsu Y., Tang M., Watanabe K., Tang Y.;
RT "Methylation-dependent acyl transfer between polyketide synthase and
RT nonribosomal peptide synthetase modules in fungal natural product
RT biosynthesis.";
RL Org. Lett. 16:6390-6393(2014).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of aspyridones (PubMed:17369821, Ref.5). The
CC polyketide-amino acid backbone preaspyridone A is first assembled by
CC the PKS-NRPS hybrid apdA (PubMed:17369821, PubMed:20828130). The
CC assembly of preaspyridone A is initiated by loading of malonyl-CoA onto
CC apdA, followed by decarboxylation to yield the acetyl starter unit
CC (PubMed:20828130). The growing polyketide chain then elongates into a
CC tetraketide (PubMed:20828130). The adpA PKS module catalyzes three
CC Claisen condensations, as well as beta-keto processing and methylation
CC (PubMed:17369821, PubMed:20828130). Alpha-methylation step during
CC polyketide synthesis is a prerequisite and a key checkpoint for chain
CC transfer between PKS and NRPS modules (PubMed:25494235). The downstream
CC NRPS module contains the condensation (C), adenylation (A), and
CC thiolation (T) domains and catalyzes the incorporation of tyrosine via
CC the formation of the L-tyrosinyl-thioester and the amide linkage
CC between L-tyrosinyl-thioester and the tetraketide (PubMed:20828130).
CC The bimodular assembly line is terminated with a reductase (R) domain
CC that facilitates formation and release of the tetramic acid product
CC (PubMed:20828130). Because apdA lacks a designated enoylreductase (ER)
CC domain, the required activity is provided the enoyl reductase apdC
CC (PubMed:17369821, PubMed:20828130, Ref.5). ApdC appears to operate with
CC different stereoselectivity in different PKS cycle (Ref.5). Combined
CC with apdC, apdA is proposed to synthesize preaspyridone A via about 20
CC enzymatic steps (PubMed:20828130). A number of oxidative steps
CC performed successively by the cytochrome P450 monooxygenases apdE and
CC apdB are required for the conversion of preaspyridone A to aspyridone A
CC (PubMed:17369821). The cytochrome P450 monooxygenase apdE is
CC responsible for the oxidative dephenylation of preaspyridone A (Ref.5).
CC Finally, the predicted FAD-dependent monooxygenase apdD and the acyl-
CC CoA dehydrogenase apdG may be involved in the transformation of
CC aspyridone A into aspyridone B (PubMed:17369821) (Probable).
CC {ECO:0000269|PubMed:17369821, ECO:0000269|PubMed:20828130,
CC ECO:0000269|PubMed:25494235, ECO:0000269|Ref.5, ECO:0000305|Ref.5}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:17369821, ECO:0000269|Ref.5}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the aspyridones
CC cluster specific transcription regulator apdR (PubMed:17369821).
CC {ECO:0000269|PubMed:17369821}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; BN001305; CBF80479.1; -; Genomic_DNA.
DR EMBL; AACD01000153; EAA67030.1; -; Genomic_DNA.
DR RefSeq; XP_681677.1; XM_676585.1.
DR AlphaFoldDB; Q5ATH2; -.
DR SMR; Q5ATH2; -.
DR STRING; 162425.CADANIAP00002882; -.
DR EnsemblFungi; CBF80479; CBF80479; ANIA_08408.
DR EnsemblFungi; EAA67030; EAA67030; AN8408.2.
DR GeneID; 2868865; -.
DR KEGG; ani:AN8408.2; -.
DR VEuPathDB; FungiDB:AN8408; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_042557_0_0_1; -.
DR InParanoid; Q5ATH2; -.
DR OMA; AFLRFGF; -.
DR OrthoDB; 825914at2759; -.
DR Proteomes; UP000000560; Chromosome V.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..498
FT /note="Cytochrome P450 monooxygenase apdB"
FT /id="PRO_0000438447"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 457
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 498 AA; 56225 MW; A5E4786DFD98F447 CRC64;
MGFVNTLTQA SDQENQRLRA SPQVFKLFVL ILFVLLVLKI RRHRANRITN QYGRQICELH
GDARVAKFAF SKQLSDQGKA LAGDEPFIIR NGRARELVVT KPEHIYDFYK GDTKPCSLLG
HAVGALAGER WSMIRRYFDP AFSFQSARQA IPELSASIDR WLDDLPLQGT GTGKGFALEI
KKPCRFLPLR LAAEFVYGEI FDDKLFSALL DLNVLHEVIL HDVIANKRLA TRLGCWFDRA
AAKRMEEFRS RWMEFNLGII QSARGASKAC PAERIYHGVE KGDLKLEEFL HTLDEILFAN
VDVSSAVLGT LFEHLAVNTA FQQKLRAEIE THIQTRTHTP DTDSDIDINT ETGKYLSKQD
TLMNFAVMEA MRLSPAFDCD FAAFSLPECT AVPKEIGGYR VPARCPVVID AKRLNADRAT
WGKDGDTYRP ERFRDIPPSK SRYGFMRFGV GAASGRCLGK HLADTLFKLT LIAVIERYSL
HSVHDGPEVE LREVVVRV
