DMXL1_CRYX8
ID DMXL1_CRYX8 Reviewed; 2299 AA.
AC A0A4P8DJE6;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Acetyl-CoA carboxylase dmxL1 {ECO:0000250|UniProtKB:Q5SWU9};
DE Short=ACC dmxL1 {ECO:0000250|UniProtKB:Q5SWU9};
DE EC=6.4.1.2 {ECO:0000250|UniProtKB:Q5SWU9};
DE AltName: Full=Dimeric xanthone biosynthesis cluster protein L1 {ECO:0000303|PubMed:30996871};
DE Includes:
DE RecName: Full=Biotin carboxylase {ECO:0000250|UniProtKB:Q5SWU9};
DE EC=6.3.4.14 {ECO:0000250|UniProtKB:Q5SWU9};
GN Name=dmxL1 {ECO:0000303|PubMed:30996871};
OS Cryptosporiopsis sp. (strain 8999).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC Helotiales; Dermateaceae; Cryptosporiopsis; unclassified Cryptosporiopsis.
OX NCBI_TaxID=2572248;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=8999;
RX PubMed=30996871; DOI=10.1039/c8sc05126g;
RA Greco C., de Mattos-Shipley K., Bailey A.M., Mulholland N.P., Vincent J.L.,
RA Willis C.L., Cox R.J., Simpson T.J.;
RT "Structure revision of cryptosporioptides and determination of the genetic
RT basis for dimeric xanthone biosynthesis in fungi.";
RL Chem. Sci. 10:2930-2939(2019).
CC -!- FUNCTION: Acetyl-CoA carboxylase; part of the gene cluster that
CC mediates the biosynthesis of the dimeric xanthones cryptosporioptides
CC (PubMed:30996871). The pathway begins with the synthesis of
CC atrochrysone thioester by the polyketide synthase dmx-nrPKS (Probable).
CC The atrochrysone carboxyl ACP thioesterase dmxR1 then breaks the
CC thioester bond and releases the atrochrysone carboxylic acid from dmx-
CC nrPKS (Probable). Atrochrysone carboxylic acid is decarboxylated by the
CC decarboxylase dmxR15, and oxidized by the anthrone oxygenase dmxR16 to
CC yield emodin (Probable). Emodin is then reduced to emodin hydroquinone
CC by the oxidoreductase dmxR7 (Probable). A-ring reduction by the short
CC chain dehydrogenase dmxR18, dehydration by the scytalone dehydratase-
CC like protein dmxR17 and probable spontaneous re-oxidation, results in
CC overall deoxygenation to chrysophanol (PubMed:30996871). Baeyer-
CC Villiger oxidation by the Baeyer-Villiger monooxygenase (BVMO) dmxR6
CC then yields monodictylactone in equilibrium with monodictyphenone
CC (PubMed:30996871). In the case of the cryptosporioptides biosynthesis,
CC monodictylactone is reduced at C-12 to an alcohol (by the short chain
CC dehydrogenases dmxR12 or dmxR8) and hydroxylated at C-5 by dmxR9,
CC yielding the electron-rich aromatic which could eliminate H(2)O to form
CC the ortho-quinonemethide, followed by tautomerisation to paraquinone
CC and complete the formal reduction to produce the 10-methylgroup
CC (Probable). Conjugate addition of C-4a-OH to the resulting paraquinone
CC by the monooxygenase dmxR10 then gives cyclohexadienone, which is then
CC reduced at C-5 by the short chain dehydrogenase dmxR3 to give the
CC dihydroxanthone (Probable). The 6,7-epoxide in the cryptosporioptides
CC could be introduced by the cytochrome P450 monooxygenase dmxL3
CC (Probable). The highly reducing PKS dmxL2 manufactures butyrate, which
CC is further carboxylated by dmxL1 to form ethylmalonate
CC (PubMed:30996871). It is not yet clear whether the carboxylation occurs
CC while the butyrate is attached to the ACP of dmxL2, but this unusual
CC fungal metabolite could then be esterified to O-5 by the O-
CC acetyltransferase dmxR13 (PubMed:30996871). Finally, dimerization
CC performed by dmxR5 gives the observed dimers cryptosporioptides A, B
CC and C as the final products of the pathway (PubMed:30996871).
CC {ECO:0000269|PubMed:30996871, ECO:0000305|PubMed:30996871}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + ATP + hydrogencarbonate = ADP + H(+) + malonyl-
CC CoA + phosphate; Xref=Rhea:RHEA:11308, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:456216; EC=6.4.1.2;
CC Evidence={ECO:0000250|UniProtKB:Q00955};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + hydrogencarbonate + N(6)-biotinyl-L-lysyl-[protein] =
CC ADP + H(+) + N(6)-carboxybiotinyl-L-lysyl-[protein] + phosphate;
CC Xref=Rhea:RHEA:13501, Rhea:RHEA-COMP:10505, Rhea:RHEA-COMP:10506,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:83144, ChEBI:CHEBI:83145,
CC ChEBI:CHEBI:456216; EC=6.3.4.14;
CC Evidence={ECO:0000250|UniProtKB:Q5SWU9};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000250|UniProtKB:O00763};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409, ECO:0000255|PROSITE-
CC ProRule:PRU00969};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30996871}.
CC -!- PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from
CC acetyl-CoA: step 1/1. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Abolished production of cryptosprioptide B and C,
CC and produces exclusively cryptosporioptide A.
CC {ECO:0000269|PubMed:30996871}.
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DR EMBL; MK182094; QCL09090.1; -; Genomic_DNA.
DR SMR; A0A4P8DJE6; -.
DR UniPathway; UPA00655; UER00711.
DR GO; GO:0003989; F:acetyl-CoA carboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004075; F:biotin carboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:2001295; P:malonyl-CoA biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.1490.20; -; 1.
DR InterPro; IPR034733; AcCoA_carboxyl.
DR InterPro; IPR013537; AcCoA_COase_cen.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR005481; BC-like_N.
DR InterPro; IPR001882; Biotin_BS.
DR InterPro; IPR011764; Biotin_carboxylation_dom.
DR InterPro; IPR005482; Biotin_COase_C.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR011763; COA_CT_C.
DR InterPro; IPR011762; COA_CT_N.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR InterPro; IPR011054; Rudment_hybrid_motif.
DR InterPro; IPR011053; Single_hybrid_motif.
DR Pfam; PF08326; ACC_central; 1.
DR Pfam; PF02785; Biotin_carb_C; 1.
DR Pfam; PF00289; Biotin_carb_N; 1.
DR Pfam; PF00364; Biotin_lipoyl; 1.
DR Pfam; PF01039; Carboxyl_trans; 1.
DR Pfam; PF02786; CPSase_L_D2; 1.
DR SMART; SM00878; Biotin_carb_C; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52096; SSF52096; 2.
DR SUPFAM; SSF52440; SSF52440; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS50979; BC; 1.
DR PROSITE; PS00188; BIOTIN; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS50989; COA_CT_CTER; 1.
DR PROSITE; PS50980; COA_CT_NTER; 1.
DR PROSITE; PS00866; CPSASE_1; 1.
DR PROSITE; PS00867; CPSASE_2; 1.
PE 3: Inferred from homology;
KW ATP-binding; Biotin; Fatty acid biosynthesis; Fatty acid metabolism;
KW Ligase; Lipid biosynthesis; Lipid metabolism; Magnesium; Manganese;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding.
FT CHAIN 1..2299
FT /note="Acetyl-CoA carboxylase dmxL1"
FT /id="PRO_0000453499"
FT DOMAIN 75..583
FT /note="Biotin carboxylation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 227..424
FT /note="ATP-grasp 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 710..784
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 1539..1887
FT /note="CoA carboxyltransferase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136"
FT DOMAIN 1891..2205
FT /note="CoA carboxyltransferase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137"
FT REGION 21..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1159..1208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1180..1200
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 258..315
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 381
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 381
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 395
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 395
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 395
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 395
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 397
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 397
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT MOD_RES 751
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
SQ SEQUENCE 2299 AA; 257833 MW; 95A4D6A15B87D549 CRC64;
MAHVNGYVLS ASASASASAP TSIPASVPAS APPSSSAPHA ARHKLADHFI GRNRVENALA
GPVKDFVKSH DGHTVITNVL IANNGIAAVK EMRSVRKWAY ETFGDERAIK FTVMATPEDL
AANADYIRMA DHYVEVPGGT NNHNYANVEL IVDIAERIDV HAVWAGWGHA SENPRLPESL
AASPKKIVFI GPPGSAMRSL GDKISSTIVA QHAKVPCIPW SGSGVDQVAI DADGIVTVDD
EVYQKGCVQS WEEGLQKAKE IGFPVMIKAS EGGGGKGIRK CEQEEGFEAL YNAASSEIPG
SPIFIMKLAG NARHLEVQLL ADQYGNNISL FGRDCSVQRR HQKIIEEAPA TVAKPEIFEA
MEKAAVRLGR LVGYVSAGTV EYLYSSADNE FYFLELNPRL QVEHPTTEMV TGVNLPAAQL
QIAMGLPLYR IHDIRLLYGV DQQAASEIDF DFSQESSFQT QQRPKPKGHT IACRITSEDP
EDGFKPSSGI VHDLNFRSSS NVWGYFSVSN TSSIHSFSDS QFGHIFAYGK TRSASRKHMV
VALKELSIRG DFRTTVEYLI KLLETPAFDN NVFTTGWLDE LITKKLTVKR PDPVLVTICG
AVCKAHLASE ASFAEYQTSL EKGQVPPIDT LKTVFPIDFI YDSYYYRFTA TRSSLDSYYL
FINGSKCSVG VRNLSDGGLL VLLDGQSHTI YWKEEIAATR LSIDGKICLL EQENDPTQLR
TSSPGKLVKY TIENGAHIKA GEAFAEVEVM KMYMPILAQE DGVVQLTKQP GTMLEPGDVL
GILTLDDPAR VKQAAQPFLN PLPDLGPPQV VGTKPAQRFR LLYNILTNIL DGFDNQFVMA
STLKELIDVL RDPELPYSEW SAQFSAFYSR IPQRLMASFT QIINRARASK SEFPAKSLSK
ALQRFREGDI VLLKSTLAPL IEVTERYDEG LKTHEFYVFS MLLEQYTAVE RQFSSRTASD
EEVILRLRDE NKNNLFKVIQ AILSHNKIRA KNNLILAILD EYKPTNLNAG NVAKYFFPAV
RKITEIESRQ VAKVALKARE VLIQCALPSV EERVVQMKHI LQSSVVESRY SETGWEYREP
VLEVLKELVD SKYTIFDVLP IFFTHQDVWV SRAALEVYVR RAYRAYSLKK VQYHNKSGDY
PHVVSWDFMR GKMGASELDM EMSSQLSTPS TPATPPTPPY ENGKQSKGVG SISDMSNLIE
NPDKEPTRKG VIVPVHDLEE AEEYLMHALQ ILPGIGERKK SHNGLLPDLA NKRQPSILGP
DGSDELSTVC NVAISDTENL DDKELLLCIQ RIVNLYKNEL LARCVRQLTF ICGHKDGTYP
GYYTFCGPEY DEDQSIRHSE PALAFQLERD RLSNFNIKPV FTTNRNIHIY EAISREMQSD
KRYFTRAVIR QGRLQDKIPT TDYLLSEASR VINDTLDALE IIGNNSSDLN HIFLNFLPVF
LSQPLEVEKA LSGLLERFRS RLWRMRVTGI EIYITYIDLL TSVAHPLRVV ITNTSGHVFQ
VEMYVEHRSE KDGKWVFQSI SSTTKIGALH LQPASTPYPT KALEWLQPKR YKAHLMGTQY
VYDFPELFRQ AIHNSWTKIV CKYPSIGEKQ PPADGYINYT EIILDDHDNL VEVVREPGTN
THGLVAWIMT ARTVEYPRGR QFMIIANDIT FRVGSFGPKE NDFFYKCTEY ARNLGIPRIY
LCANSGARIG IAEELVPYFN VAWNNPENPE AGFKYLYLTP EDKKKFETQG VVTEEVIENR
ETRYKIIMIA DAKDGHGMDC LKGSALIAAV TSRAYEDIFT ITLVTCRSVA ACHAHPLLGI
GSYLVRLGQR AIQIEGHPMI LTGAPAINKV LGQEVYTSNL QLGGTQIMYK NGVSHMTVND
DFEGVSKIVE WLAFVPEKKN TLVPIGPMID PWDRDIVCSP SKQSYDVRCL IEGMETADGF
QSGFFDRDSF VESLGGWAKT VVVGRARLGG IPMGIIAVET RTVENITPAN PANGNSTEQI
AIEAGGVWYP NSAFKTAQAI KDFNHGEQLP LMVLANWRGF SGGQKDMYDE ILKYGSYILD
AFIKYEQPVF VYIPPFAQVR GGSWVVLDPV LNQEFMEMYA DEDARCGILE PEGVVNVRYR
QDKQLETMAR LDPEYRALRQ KLADPSLSKE EMDDTKAKAT AREQLLLPIY LQVSLQFADL
HDRAGCMTAK HLIRTELKWR DARRFFYWRV RRRVLEEHIL KRIATSSKNP RINRGRNLAS
LAAWTGIPNF STADREVALW YEENQKLVDE KVENLKTEGV AYDVASLLRV DSKGGLKGVR
HVLSMLSAKE REEALQFLN
