AATA_PENRW
ID AATA_PENRW Reviewed; 357 AA.
AC B6HLT9;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Isopenicillin-N N-acyltransferase {ECO:0000303|PubMed:2120195};
DE Short=IAT {ECO:0000303|PubMed:2120195};
DE Short=IPN acyltransferase {ECO:0000303|PubMed:2120195};
DE EC=2.3.1.164 {ECO:0000269|PubMed:1368505, ECO:0000269|PubMed:2110531, ECO:0000269|PubMed:2120195};
DE AltName: Full=Acyl-coenzyme A:6-aminopenicillanic-acid-acyltransferase 40 kDa form {ECO:0000303|PubMed:1368505};
DE AltName: Full=Penicillin biosynthetis cluster protein aatA {ECO:0000303|PubMed:1368505};
DE Contains:
DE RecName: Full=Acyl-coenzyme A:6-aminopenicillanic acid acyltransferase 11 kDa subunit {ECO:0000250|UniProtKB:P15802};
DE Contains:
DE RecName: Full=Acyl-coenzyme A:6-aminopenicillanic acid acyltransferase 29 kDa subunit {ECO:0000250|UniProtKB:P15802};
GN Name=aatA {ECO:0000303|PubMed:1368505}; ORFNames=PCH_Pc21g21370;
OS Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS 54-1255) (Penicillium chrysogenum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC Penicillium chrysogenum species complex.
OX NCBI_TaxID=500485;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX PubMed=18820685; DOI=10.1038/nbt.1498;
RA van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA Bovenberg R.A.L.;
RT "Genome sequencing and analysis of the filamentous fungus Penicillium
RT chrysogenum.";
RL Nat. Biotechnol. 26:1161-1168(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=1368505; DOI=10.1038/nbt0190-39;
RA Smith D.J., Burnham M.K., Edwards J., Earl A.J., Turner G.;
RT "Cloning and heterologous expression of the penicillin biosynthetic gene
RT cluster from penicillum chrysogenum.";
RL Biotechnology (N.Y.) 8:39-41(1990).
RN [3]
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=2110531; DOI=10.1016/0014-5793(90)80224-7;
RA Whiteman P.A., Abraham E.P., Baldwin J.E., Fleming M.D., Schofield C.J.,
RA Sutherland J.D., Willis A.C.;
RT "Acyl coenzyme A: 6-aminopenicillanic acid acyltransferase from Penicillium
RT chrysogenum and Aspergillus nidulans.";
RL FEBS Lett. 262:342-344(1990).
RN [4]
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=2120195; DOI=10.1128/jb.172.10.5908-5914.1990;
RA Tobin M.B., Fleming M.D., Skatrud P.L., Miller J.R.;
RT "Molecular characterization of the acyl-coenzyme A:isopenicillin N
RT acyltransferase gene (penDE) from Penicillium chrysogenum and Aspergillus
RT nidulans and activity of recombinant enzyme in Escherichia coli.";
RL J. Bacteriol. 172:5908-5914(1990).
RN [5]
RP FUNCTION.
RX PubMed=1369045; DOI=10.1002/jctb.280550306;
RA Bainbridge Z.A., Scott R.I., Perry D.;
RT "Oxygen utilisation by isopenicillin N synthase from Penicillium
RT chrysogenum.";
RL J. Chem. Technol. Biotechnol. 55:233-238(1992).
RN [6]
RP FUNCTION.
RX PubMed=1588566; DOI=10.1021/jm00088a028;
RA Huffman G.W., Gesellchen P.D., Turner J.R., Rothenberger R.B.,
RA Osborne H.E., Miller F.D., Chapman J.L., Queener S.W.;
RT "Substrate specificity of isopenicillin N synthase.";
RL J. Med. Chem. 35:1897-1914(1992).
RN [7]
RP POST-TRANSLATIONAL CLEAVAGE.
RX PubMed=8396910; DOI=10.1042/bj2940357;
RA Aplin R.T., Baldwin J.E., Roach P.L., Robinson C.V., Schofield C.J.;
RT "Investigations into the post-translational modification and mechanism of
RT isopenicillin N:acyl-CoA acyltransferase using electrospray mass
RT spectrometry.";
RL Biochem. J. 294:357-363(1993).
RN [8]
RP FUNCTION.
RX PubMed=8416970; DOI=10.1016/s0021-9258(18)54203-4;
RA Lendenfeld T., Ghali D., Wolschek M., Kubicek-Pranz E.M., Kubicek C.P.;
RT "Subcellular compartmentation of penicillin biosynthesis in Penicillium
RT chrysogenum. The amino acid precursors are derived from the vacuole.";
RL J. Biol. Chem. 268:665-671(1993).
RN [9]
RP FUNCTION.
RX PubMed=9266851; DOI=10.1006/bbrc.1997.7107;
RA Etchegaray A., Dieckmann R., Kennedy J., Turner G., von Doehren H.;
RT "ACV synthetase: expression of amino acid activating domains of the
RT Penicillium chrysogenum enzyme in Aspergillus nidulans.";
RL Biochem. Biophys. Res. Commun. 237:166-169(1997).
RN [10]
RP FUNCTION.
RX PubMed=9355751; DOI=10.1042/bj3270185;
RA Theilgaard H.B., Kristiansen K.N., Henriksen C.M., Nielsen J.;
RT "Purification and characterization of delta-(L-alpha-aminoadipyl)-L-
RT cysteinyl-D-valine synthetase from Penicillium chrysogenum.";
RL Biochem. J. 327:185-191(1997).
RN [11]
RP SELF-PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=18439860; DOI=10.1016/j.fgb.2008.03.005;
RA Garcia-Estrada C., Vaca I., Fierro F., Sjollema K., Veenhuis M.,
RA Martin J.F.;
RT "The unprocessed preprotein form IATC103S of the isopenicillin N
RT acyltransferase is transported inside peroxisomes and regulates its self-
RT processing.";
RL Fungal Genet. Biol. 45:1043-1052(2008).
RN [12]
RP FUNCTION.
RX PubMed=19686863; DOI=10.1016/j.ymben.2009.08.002;
RA Siewers V., Chen X., Huang L., Zhang J., Nielsen J.;
RT "Heterologous production of non-ribosomal peptide LLD-ACV in Saccharomyces
RT cerevisiae.";
RL Metab. Eng. 11:391-397(2009).
RN [13]
RP SELF-PROCESSING.
RX PubMed=20223213; DOI=10.1016/j.str.2010.01.005;
RA Bokhove M., Yoshida H., Hensgens C.M., van der Laan J.M., Sutherland J.D.,
RA Dijkstra B.W.;
RT "Structures of an isopenicillin N converting Ntn-hydrolase reveal different
RT catalytic roles for the active site residues of precursor and mature
RT enzyme.";
RL Structure 18:301-308(2010).
RN [14]
RP FUNCTION.
RX PubMed=21889568; DOI=10.1016/j.biochi.2011.08.002;
RA Wu X., Garcia-Estrada C., Vaca I., Martin J.F.;
RT "Motifs in the C-terminal region of the Penicillium chrysogenum ACV
RT synthetase are essential for valine epimerization and processivity of
RT tripeptide formation.";
RL Biochimie 94:354-364(2012).
RN [15]
RP INDUCTION.
RX PubMed=22960281; DOI=10.1016/j.fgb.2012.08.002;
RA Dominguez-Santos R., Martin J.F., Kosalkova K., Prieto C., Ullan R.V.,
RA Garcia-Estrada C.;
RT "The regulatory factor PcRFX1 controls the expression of the three genes of
RT beta-lactam biosynthesis in Penicillium chrysogenum.";
RL Fungal Genet. Biol. 49:866-881(2012).
RN [16]
RP FUNCTION.
RX PubMed=22777282; DOI=10.1007/s00253-012-4256-0;
RA Fernandez-Aguado M., Teijeira F., Martin J.F., Ullan R.V.;
RT "A vacuolar membrane protein affects drastically the biosynthesis of the
RT ACV tripeptide and the beta-lactam pathway of Penicillium chrysogenum.";
RL Appl. Microbiol. Biotechnol. 97:795-808(2013).
RN [17]
RP FUNCTION.
RX PubMed=23053082; DOI=10.1007/s00253-012-4425-1;
RA Fernandez-Aguado M., Ullan R.V., Teijeira F., Rodriguez-Castro R.,
RA Martin J.F.;
RT "The transport of phenylacetic acid across the peroxisomal membrane is
RT mediated by the PaaT protein in Penicillium chrysogenum.";
RL Appl. Microbiol. Biotechnol. 97:3073-3084(2013).
RN [18]
RP FUNCTION.
RX PubMed=24480587; DOI=10.1016/j.ymben.2014.01.004;
RA Fernandez-Aguado M., Martin J.F., Rodriguez-Castro R., Garcia-Estrada C.,
RA Albillos S.M., Teijeira F., Ullan R.V.;
RT "New insights into the isopenicillin N transport in Penicillium
RT chrysogenum.";
RL Metab. Eng. 22:89-103(2014).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of penicillin, the world's most
CC important antibiotic (PubMed:1368505, PubMed:2120195, PubMed:2110531).
CC The first step of the pathway is performed by the trimodular NRPS acvA
CC that produces the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-
CC cysteinyl-D-valine (LLD-ACV or ACV) via condensation of the 3 residues
CC L-2-aminoadipate, L-cysteine and L-valine (PubMed:9266851,
CC PubMed:9355751, PubMed:19686863, PubMed:21889568). The precursor amino
CC acids for penicillin biosynthesis are withdrawn from the vacuolar amino
CC acid pool by the MFS-type transporter penV (PubMed:8416970,
CC PubMed:22777282). Each of the constituent amino acids of the tripeptide
CC acv are activated as aminoacyl-adenylates with peptide bonds formed
CC through the participation of amino acid thioester intermediates
CC (PubMed:9266851, PubMed:21889568). The tripeptide ACV is then cyclized
CC to form isopenicillin N (IPN) by the isopenicillin N synthase ipnA that
CC forms the beta-lactam nucleus (PubMed:1368505, PubMed:1369045,
CC PubMed:1588566). Finally, the alpha-aminoadipyl side chain is exchanged
CC for phenylacetic acid by the isopenicillin N acyltransferase aatA to
CC yield penicillin (PubMed:2120195, PubMed:2110531, PubMed:1368505). This
CC step occurs in the peroxisomal matrix and the penM and paaT
CC transporters are involved in the isopenicillin N and phenylacetic acid
CC import into the peroxisome, respectively (PubMed:23053082).
CC {ECO:0000269|PubMed:1368505, ECO:0000269|PubMed:1369045,
CC ECO:0000269|PubMed:1588566, ECO:0000269|PubMed:19686863,
CC ECO:0000269|PubMed:2110531, ECO:0000269|PubMed:2120195,
CC ECO:0000269|PubMed:21889568, ECO:0000269|PubMed:22777282,
CC ECO:0000269|PubMed:23053082, ECO:0000269|PubMed:8416970,
CC ECO:0000269|PubMed:9266851, ECO:0000269|PubMed:9355751}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + isopenicillin N + phenylacetyl-CoA = CoA + H(+) + L-2-
CC aminoadipate + penicillin G; Xref=Rhea:RHEA:20720, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:51354, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57390, ChEBI:CHEBI:58399, ChEBI:CHEBI:58672;
CC EC=2.3.1.164; Evidence={ECO:0000269|PubMed:1368505,
CC ECO:0000269|PubMed:2110531, ECO:0000269|PubMed:2120195};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20721;
CC Evidence={ECO:0000269|PubMed:1368505, ECO:0000269|PubMed:2110531,
CC ECO:0000269|PubMed:2120195};
CC -!- PATHWAY: Antibiotic biosynthesis; penicillin G biosynthesis; penicillin
CC G from L-alpha-aminoadipate and L-cysteine and L-valine: step 3/3.
CC {ECO:0000269|PubMed:1368505, ECO:0000269|PubMed:2110531,
CC ECO:0000269|PubMed:2120195}.
CC -!- SUBUNIT: The active form of the enzyme results from processing of the
CC 40-kDa monomeric precursor to a heterodimer containing subunits of 11
CC and 29 kDa. {ECO:0000269|PubMed:2110531, ECO:0000269|PubMed:2120195}.
CC -!- SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000269|PubMed:18439860}.
CC Note=The unprocessed preprotein is translocated inside peroxisomes and
CC regulates its self-processing. {ECO:0000269|PubMed:18439860}.
CC -!- INDUCTION: The transcription factor rfx1 controls penicillin
CC biosynthesis through the regulation of the acvA, ipnA and aatA
CC transcription. {ECO:0000269|PubMed:22960281}.
CC -!- PTM: The pre-AAT protein is synthesized as 40 kDa precursor which is
CC then self-processed into an 11 kDa (protein A) and a 29 kDa (protein
CC B). The B protein carries AAT activity. {ECO:0000269|PubMed:18439860,
CC ECO:0000269|PubMed:20223213, ECO:0000269|PubMed:2120195,
CC ECO:0000269|PubMed:8396910}.
CC -!- SIMILARITY: Belongs to the peptidase C45 family. {ECO:0000305}.
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DR EMBL; AM920436; CAP97034.1; -; Genomic_DNA.
DR RefSeq; XP_002569112.1; XM_002569066.1.
DR SMR; B6HLT9; -.
DR STRING; 1108849.XP_002569112.1; -.
DR MEROPS; C45.001; -.
DR EnsemblFungi; CAP97034; CAP97034; PCH_Pc21g21370.
DR GeneID; 8304967; -.
DR KEGG; pcs:Pc21g21370; -.
DR VEuPathDB; FungiDB:PCH_Pc21g21370; -.
DR eggNOG; ENOG502RY9N; Eukaryota.
DR HOGENOM; CLU_037787_1_0_1; -.
DR OMA; NWDFFSA; -.
DR OrthoDB; 872824at2759; -.
DR UniPathway; UPA00149; UER00241.
DR Proteomes; UP000000724; Contig Pc00c21.
DR GO; GO:0005782; C:peroxisomal matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0042318; P:penicillin biosynthetic process; IDA:GO_Central.
DR InterPro; IPR005079; Peptidase_C45.
DR Pfam; PF03417; AAT; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Peroxisome; Reference proteome; Transferase.
FT CHAIN 1..357
FT /note="Isopenicillin-N N-acyltransferase"
FT /id="PRO_0000455269"
FT CHAIN 1..102
FT /note="Acyl-coenzyme A:6-aminopenicillanic acid
FT acyltransferase 11 kDa subunit"
FT /id="PRO_0000455270"
FT CHAIN 103..357
FT /note="Acyl-coenzyme A:6-aminopenicillanic acid
FT acyltransferase 29 kDa subunit"
FT /id="PRO_0000455271"
FT BINDING 121
FT /ligand="6-aminopenicillanate"
FT /ligand_id="ChEBI:CHEBI:57869"
FT /evidence="ECO:0000269|PubMed:20223213"
FT BINDING 310
FT /ligand="6-aminopenicillanate"
FT /ligand_id="ChEBI:CHEBI:57869"
FT /evidence="ECO:0000269|PubMed:20223213"
SQ SEQUENCE 357 AA; 39939 MW; 7A05822312D1CF08 CRC64;
MLHILCQGTP FEIGYEHGSA AKAVIARSID FAVDLIRGKT KKTDEELKQV LSQLGRVIEE
RWPKYYEEIR GIAKGAERDV SEIVMLNTRT EFAYGLKAAR DGCTTAYCQL PNGALQGQNW
DFFSATKENL IRLTIRQAGL PTIKFITEAG IIGKVGFNSA GVAVNYNALH LQGLRPTGVP
SHIALRIALE STSPSQAYDR IVEQGGMAAS AFIMVGNGHE AFGLEFSPTS IRKQVLDANG
RMVHTNHCLL QHGKNEKELD PLPDSWNRHQ RMEFLLDGFD GTKQAFAQLW ADEDNYPFSI
CRAYEEGKSR GATLFNIIYD HARREATVRL GRPTNPDEMF VMRFDEEDER SALNARL
