AC891_PENBR
ID AC891_PENBR Reviewed; 707 AA.
AC P9WEY3;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Acyl-CoA ligase 891, peroxisomal {ECO:0000303|PubMed:31209052};
DE Short=ACL891 {ECO:0000303|PubMed:31209052};
DE EC=6.2.1.- {ECO:0000269|PubMed:31209052};
OS Penicillium brevicompactum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5074;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RX PubMed=31209052; DOI=10.1073/pnas.1821932116;
RA Zhang W., Du L., Qu Z., Zhang X., Li F., Li Z., Qi F., Wang X., Jiang Y.,
RA Men P., Sun J., Cao S., Geng C., Qi F., Wan X., Liu C., Li S.;
RT "Compartmentalized biosynthesis of mycophenolic acid.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:13305-13310(2019).
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
CC (PubMed:31209052). The peroxisomal acyl-CoA ligase 891 converts the
CC intermediate MFDHMP-3C into MFDHMP-3C-CoA which impairs its diffusion
CC from the peroxisome (PubMed:31209052). 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 (PubMed:31209052) (Probable).
CC {ECO:0000269|PubMed:31209052, ECO:0000305|PubMed:31209052}.
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:0000269|PubMed:31209052};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66701;
CC Evidence={ECO:0000269|PubMed:31209052};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31209052}.
CC -!- SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000269|PubMed:31209052}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR AlphaFoldDB; P9WEY3; -.
DR SMR; P9WEY3; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IDA:GO_Central.
DR GO; GO:0140722; P:mycophenolic acid biosynthetic process; IDA: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 1: Evidence at protein level;
KW ATP-binding; Ligase; Magnesium; Nucleotide-binding; Peroxisome.
FT CHAIN 1..707
FT /note="Acyl-CoA ligase 891, peroxisomal"
FT /id="PRO_0000451896"
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:0000305|PubMed:31209052"
FT BINDING 259..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 707 AA; 78110 MW; E98D758B99370A5E CRC64;
MFFTQPPHLV KAEELKQEPP KGTAYSVAIP GTEQPGRSRV YRAWNAQKEL LTTLDPQVTT
AHDMFESTAN RQPKNHCLGW RPYNSTTKTW DPYQWLTYET VQKRRAAFGA GLVELHQKHN
CHRPGQYGVG LWAQNRPEWQ ITDLACISQS LYSVSIYDVL APDATEYIIN HAELNCVVTS
LPHIPTLLKL KSSLPNLKMI VSLDPLDGPE QNGHSKRALL ESMAAGLDLA IYTIDQVEEL
GLASKRGYNA PSASDIVTIN YTSGTTGPPK GVVLTHGNAV AATSCGLTTI GQARGDTMCS
YLPLAHIYAR LAEHTAFWGG ARIGYFHGNI VELVDDLKLL KPTGFMSVPR LYSRFGTAIR
AATVEQPGFK GALSRHIVAA KMANMKNPDP SKATIKHALY DRIWAKKVAA ALGLERAKYM
ISGSAPLDPT LHNFLRVATG TDVVQGYGLT ESYASATAQS TQDLSSGNCG RLAPCTEACL
VSLPDMEYSV EDKPFPRGEL LLRGNNMFRE YYKNDDETSK AVTEDGWFRT GDVCTVDAQG
RFIIIDRRKN VLKLAQGEYI SPERLEGVIL SELGYVAQAY VHGDSSETFL VGIFGVAPDL
FAPYASKVLG KTIAPTDVEG LKEHLNDDKL RRAVLRDLER VAKKHKFAGY ERVRNVSLKV
DPFTVENNLL TPTLKLKRPP VVKMYRTLLD QLYGQANEEQ SAPRAKL
