AC891_PENRF
ID AC891_PENRF Reviewed; 707 AA.
AC W6R1D9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Acyl-CoA ligase 891, peroxisomal {ECO:0000250|UniProtKB:P9WEY3};
DE Short=ACL891 {ECO:0000250|UniProtKB:P9WEY3};
DE EC=6.2.1.- {ECO:0000250|UniProtKB:P9WEY3};
GN ORFNames=PROQFM164_S04g000523;
OS Penicillium roqueforti (strain FM164).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=1365484;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FM164;
RX PubMed=24407037; DOI=10.1038/ncomms3876;
RA Cheeseman K., Ropars J., Renault P., Dupont J., Gouzy J., Branca A.,
RA Abraham A.L., Ceppi M., Conseiller E., Debuchy R., Malagnac F., Goarin A.,
RA Silar P., Lacoste S., Sallet E., Bensimon A., Giraud T., Brygoo Y.;
RT "Multiple recent horizontal transfers of a large genomic region in cheese
RT making fungi.";
RL Nat. Commun. 5:2876-2876(2014).
CC -!- FUNCTION: Acyl-CoA ligase involved in the biosynthesis of mycophenolic
CC acid (MPA), the first isolated antibiotic natural product in the world
CC obtained from a culture of Penicillium brevicompactum in 1893 (By
CC similarity). The peroxisomal acyl-CoA ligase 891 converts the
CC intermediate MFDHMP-3C into MFDHMP-3C-CoA which impairs its diffusion
CC from the peroxisome (By similarity). The first step of the pathway is
CC the synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic
CC polyketide synthase mpaC. 5MOA is then converted to the phthalide
CC compound 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) by the endoplasmic
CC reticulum-bound cytochrome P450 monooxygenase mpaDE. MpaDE first
CC catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-
CC methylbenzoic acid (DHMB). MpaDE then acts as a lactone synthase that
CC catalyzes the ring closure to convert DHMB into DHMP. The next step is
CC the prenylation of DHMP by the Golgi apparatus-associated
CC prenyltransferase mpaA to yield farnesyl-DHMP (FDHMP). The ER-bound
CC oxygenase mpaB then mediates the oxidative cleavage the C19-C20 double
CC bond in FDHMP to yield FDHMP-3C via a mycophenolic aldehyde
CC intermediate. The O-methyltransferase mpaG catalyzes the methylation of
CC FDHMP-3C to yield MFDHMP-3C. After the cytosolic methylation of FDHMP-
CC 3C, MFDHMP-3C enters into peroxisomes probably via free diffusion due
CC to its low molecular weight. Upon a peroxisomal CoA ligation reaction,
CC catalyzed by a beta-oxidation component enzyme acyl-CoA ligase ACL891,
CC MFDHMP-3C-CoA would then be restricted to peroxisomes for the following
CC beta-oxidation pathway steps. The peroxisomal beta-oxidation machinery
CC than converts MFDHMP-3C-CoA into MPA_CoA, via a beta-oxidation chain-
CC shortening process. Finally mpaH acts as a peroxisomal acyl-CoA
CC hydrolase with high substrate specificity toward MPA-CoA to release the
CC final product MPA (By similarity). {ECO:0000250|UniProtKB:P9WEY3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4E,8E)-10-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-
CC benzofuran-5-yl)-4,8-dimethyldeca-4,8-dienoate + ATP + CoA = (4E,8E)-
CC 10-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-
CC yl)-4,8-dimethyldeca-4,8-dienoyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:66700, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:167390, ChEBI:CHEBI:167446,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P9WEY3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66701;
CC Evidence={ECO:0000250|UniProtKB:P9WEY3};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000250|UniProtKB:P9WEY3}.
CC -!- SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000250|UniProtKB:P9WEY3}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; HG792018; CDM35642.1; -; Genomic_DNA.
DR AlphaFoldDB; W6R1D9; -.
DR SMR; W6R1D9; -.
DR STRING; 1365484.W6R1D9; -.
DR EnsemblFungi; CDM35642; CDM35642; PROQFM164_S04g000523.
DR OrthoDB; 630541at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000030686; Unassembled WGS sequence.
DR GO; GO:0005782; C:peroxisomal matrix; ISS:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; ISS:GO_Central.
DR GO; GO:0140722; P:mycophenolic acid biosynthetic process; ISS:GO_Central.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 3: Inferred from homology;
KW ATP-binding; Ligase; Nucleotide-binding; Peroxisome.
FT CHAIN 1..707
FT /note="Acyl-CoA ligase 891, peroxisomal"
FT /id="PRO_0000451897"
FT REGION 525..549
FT /note="Fatty acid-binding"
FT /evidence="ECO:0000255"
FT MOTIF 705..707
FT /note="Peroxisome targeting signal"
FT /evidence="ECO:0000250|UniProtKB:P9WEY3"
FT BINDING 259..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 707 AA; 77898 MW; D07B7E46DE4083DA CRC64;
MFFSQPTHLA KAEELKQAPP KGVAYSVALP GTEQPGRSPV YRAWNAQKEL LTTLDPEVTT
AHDIFESTAI RHPKNDCLGW RPYNSTTKSF DPYQWLTYET VQKRRAAFGA GIVELHHKHD
CHRPGQYGVG LWSQNRPEWQ ITDLACVSQS LYSVSIYDVL SEDATEYIIN HSELSCVVTS
LPHIASLIKL KPSLPTLKII ISLDPLDGGE QAGHSKRAIF ESMAAGLGLA IYTIDQVEEL
GLASKRGYNP PSASDIVTIN YTSGTTGPPK GVVLTHGNAV AATSCGLITI SQARGDTSAS
YLPLAHIYAR LAEHTAFWGA ARIGYFHGNI AELVDDLKLL KPTGFMSVPR LYSRFGSAIR
AATVEQPGFK GALSRHIIAA KTANMKNPDP SKATVRHALY DRIWAKKVTA ALGLERARYM
VSGSAPLDPT LHNFLRVATG TDVLQGYGLT ESYASATAQP VYDLTAGNCG SLAPCVEACL
VSLPDMEYSV DDKPFPRGEL LLRGNNMFRE YYKNEEETRS AITEDGWFRT GDVCTIDEKG
RFIIIDRRKN VLKLAQGEYI SPERLEGVVL SELGYIAQAY VHGDSLQTFL VGIFGVAPDL
FAPYASKVLG RTIAPTDLEA VKESLNDDKV RRAVLRDLER VAKKHKFAGY ERIRNVSLKV
EPFTVENNLL TPTLKLKRPP TVKVYRSLLD QLYEQAVEEQ SAPKAKL
