AATA_PENCH
ID AATA_PENCH Reviewed; 357 AA.
AC P15802;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 92.
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:2555269};
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:0000303|PubMed:2555269};
DE Contains:
DE RecName: Full=Acyl-coenzyme A:6-aminopenicillanic acid acyltransferase 29 kDa subunit {ECO:0000303|PubMed:2555269};
GN Name=aatA {ECO:0000303|PubMed:2555269};
GN Synonyms=penDE {ECO:0000303|PubMed:2120195};
OS Penicillium chrysogenum (Penicillium notatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC Penicillium chrysogenum species complex.
OX NCBI_TaxID=5076;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-31 AND
RP 104-129.
RC STRAIN=AS-P-78;
RX PubMed=2555269; DOI=10.1016/0378-1119(89)90115-7;
RA Barredo J.L., van Solingen P., Diez B., Alvarez E., Cantoral J.M.,
RA Kattevilder A., Smaal E.B., Groenen M.A.M., Veenstra A.E., Martin J.F.;
RT "Cloning and characterization of the acyl-coenzyme A: 6-aminopenicillanic-
RT acid-acyltransferase gene of Penicillium chrysogenum.";
RL Gene 83:291-300(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBUNIT, CATALYTIC ACTIVITY,
RP 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 [3]
RP PROTEIN SEQUENCE OF 1-20; 103-131; 188-200; 258-265 AND 316-323, FUNCTION,
RP 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, 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 [5]
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 [6]
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 [7]
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 [8]
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 [9] {ECO:0007744|PDB:2X1C, ECO:0007744|PDB:2X1D, ECO:0007744|PDB:2X1E}
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) IN COMPLEX WITH 6-AMINOPENICILLANIC
RP ACID, AND 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).
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:2120195, PubMed:2110531, PubMed:1368505).
CC AatA catalyzes the exchange of the alpha-aminoadipyl side chain of
CC isopenicillin N for phenylacetic acid to yield penicillin
CC (PubMed:2120195, PubMed:2110531, PubMed:1368505). This step occurs in
CC the peroxisomal matrix and the penM and paaT transporters are involved
CC in the isopenicillin N and phenylacetic acid import into the
CC peroxisome, respectively (PubMed:23053082). The penicillin biosynthesis
CC occurs via 3 enzymatic steps, the first corresponding to the production
CC of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-
CC valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then
CC cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA
CC that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side
CC chain is exchanged for phenylacetic acid by the isopenicillin N
CC acyltransferase aatA to yield penicillin in the peroxisomal matrix
CC (PubMed:1368505) (Probable). {ECO:0000269|PubMed:1368505,
CC ECO:0000269|PubMed:2110531, ECO:0000269|PubMed:2120195,
CC ECO:0000269|PubMed:23053082, ECO:0000305|PubMed:1368505}.
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; M31454; AAA33692.1; -; Genomic_DNA.
DR EMBL; A15528; CAA01234.1; -; Genomic_DNA.
DR EMBL; A15359; CAA01221.1; -; Genomic_DNA.
DR PIR; JQ0118; JQ0118.
DR PDB; 2X1C; X-ray; 1.85 A; A/B/C/D=1-357.
DR PDB; 2X1D; X-ray; 1.64 A; A/B/C/D=1-357.
DR PDB; 2X1E; X-ray; 2.00 A; A/B/C/D=1-357.
DR PDBsum; 2X1C; -.
DR PDBsum; 2X1D; -.
DR PDBsum; 2X1E; -.
DR AlphaFoldDB; P15802; -.
DR SMR; P15802; -.
DR MEROPS; C45.001; -.
DR PhylomeDB; P15802; -.
DR BioCyc; MetaCyc:MON-13369; -.
DR BRENDA; 2.3.1.164; 4606.
DR UniPathway; UPA00149; UER00241.
DR EvolutionaryTrace; P15802; -.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:GO_Central.
DR GO; GO:0102920; F:acyl coenzyme A: isopenicillin N acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0050640; F:isopenicillin-N N-acyltransferase activity; IDA:GO_Central.
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 3D-structure; Acyltransferase; Antibiotic biosynthesis;
KW Direct protein sequencing; Peroxisome; Transferase; Zymogen.
FT CHAIN 1..357
FT /note="Isopenicillin-N N-acyltransferase"
FT /id="PRO_0000020595"
FT CHAIN 1..102
FT /note="Acyl-coenzyme A:6-aminopenicillanic acid
FT acyltransferase 11 kDa subunit"
FT /id="PRO_0000020596"
FT CHAIN 103..357
FT /note="Acyl-coenzyme A:6-aminopenicillanic acid
FT acyltransferase 29 kDa subunit"
FT /id="PRO_0000020597"
FT BINDING 121
FT /ligand="6-aminopenicillanate"
FT /ligand_id="ChEBI:CHEBI:57869"
FT /evidence="ECO:0000269|PubMed:20223213,
FT ECO:0007744|PDB:2X1E"
FT BINDING 310
FT /ligand="6-aminopenicillanate"
FT /ligand_id="ChEBI:CHEBI:57869"
FT /evidence="ECO:0000269|PubMed:20223213,
FT ECO:0007744|PDB:2X1E"
FT CONFLICT 103
FT /note="C -> W (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="A -> P (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 10..20
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 22..37
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 44..61
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 63..76
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 80..87
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 89..100
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 115..122
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 124..129
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 130..136
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 181..189
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 194..203
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 263..277
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 283..289
FT /evidence="ECO:0007829|PDB:2X1D"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:2X1D"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 312..320
FT /evidence="ECO:0007829|PDB:2X1D"
FT TURN 321..324
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:2X1D"
FT STRAND 337..343
FT /evidence="ECO:0007829|PDB:2X1D"
FT HELIX 346..353
FT /evidence="ECO:0007829|PDB:2X1D"
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
