UniProtKB - Q12053 (AFLC_ASPPU)
Norsolorinic acid synthase
aflC
Functioni
Norsolorinic acid synthase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:7592391, PubMed:15094053, PubMed:7565588, PubMed:15006741).
The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741).
The first step of the pathway is the conversion of acetate to norsolorinic acid (NOR) and requires the fatty acid synthase subunits aflA and aflB, as well as the PKS aflC (PubMed:15006741).
AflC combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor NOR (PubMed:17086560, PubMed:18403714).
The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase aflA/aflB (PubMed:16256699).
The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin (PubMed:10584035).
The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN (PubMed:15006741).
The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN) (PubMed:8368836).
The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway (PubMed:15006741, PubMed:11055914, PubMed:15932995).
The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA) (PubMed:15006741).
VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL) (PubMed:15006741).
Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA-binding, thus giving to aflatoxin its activity as a mutagen (PubMed:15006741, PubMed:8368837, PubMed:15932995).
Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA) (PubMed:15006741, PubMed:8368837).
A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2 (PubMed:15006741).
Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST) (PubMed:15006741, PubMed:1339261, PubMed:15771506).
AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring (PubMed:16332900, PubMed:16461654).
The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST) (PubMed:10543813).
Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively (PubMed:8434913).
Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741, PubMed:11996570, PubMed:15528514, PubMed:18486503).
2 Publications20 PublicationsCatalytic activityi
- 6 H+ + hexanoyl-[ACP] + 7 malonyl-CoA = 7 CO2 + 7 CoA + 2 H2O + holo-[ACP] + noranthrone1 PublicationEC:2.3.1.2211 Publication
Cofactori
: aflatoxin biosynthesis Pathwayi
This protein is involved in the pathway aflatoxin biosynthesis, which is part of Mycotoxin biosynthesis.1 Publication1 PublicationView all proteins of this organism that are known to be involved in the pathway aflatoxin biosynthesis and in Mycotoxin biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 543 | For beta-ketoacyl synthase activityBy similarity | 1 | |
Active sitei | 993 | For acyl/malonyl transferase activityBy similarity | 1 | |
Active sitei | 1937 | For thioesterase activity1 Publication | 1 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- norsolorinate anthrone synthase activity Source: UniProtKB-EC
- phosphopantetheine binding Source: InterPro
GO - Biological processi
- aflatoxin biosynthetic process Source: UniProtKB-UniPathway
Keywordsi
Molecular function | Acyltransferase, Multifunctional enzyme, Transferase |
Enzyme and pathway databases
BRENDAi | 2.3.1.221, 523 |
UniPathwayi | UPA00287 |
Protein family/group databases
ESTHERi | aspor-PKSL1, Thioesterase |
Names & Taxonomyi
Protein namesi | Recommended name: Norsolorinic acid synthase1 Publication (EC:2.3.1.2212 Publications)Short name: NSAS1 Publication Alternative name(s): Aflatoxin biosynthesis polyketide synthaseCurated Aflatoxin biosynthesis protein C1 Publication Polyketide synthase A1 Publication |
Gene namesi | Name:aflC1 Publication Synonyms:pksA1 Publication, pksL11 Publication ORF Names:P875_00052995 |
Organismi | Aspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1) |
Taxonomic identifieri | 1403190 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Aspergillaceae › Aspergillus › |
Proteomesi |
|
Pathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1345 | H → A: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 1491 | G → L: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 1543 | D → A: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 1546 | T → A: 40% decrease in catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 1547 | Q → A: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 1554 | N → A: Abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 1937 | S → A: Abolishes hydrolytic activity. 1 Publication | 1 | |
Mutagenesisi | 1964 | D → N: Abolishes hydrolytic activity. 1 Publication | 1 | |
Mutagenesisi | 2070 | D → N: Slight reduction in hydrolytic activity. 1 Publication | 1 | |
Mutagenesisi | 2088 | H → F: Abolishes hydrolytic activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000180303 | 1 – 2109 | Norsolorinic acid synthaseAdd BLAST | 2109 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1746 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation1 Publication | 1 |
Keywords - PTMi
Phosphopantetheine, PhosphoproteinExpressioni
Inductioni
Interactioni
Binary interactionsi
Q12053
With | #Exp. | IntAct |
---|---|---|
itself | 4 | EBI-15811477,EBI-15811477 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
DIPi | DIP-59286N |
STRINGi | 1403190.Q12053 |
Structurei
Secondary structure
3D structure databases
BMRBi | Q12053 |
SMRi | Q12053 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q12053 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1709 – 1788 | CarrierPROSITE-ProRule annotation1 PublicationAdd BLAST | 80 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 374 | Starter unit:ACP transacylase (SAT) domainSequence analysisAdd BLAST | 374 | |
Regioni | 363 – 819 | Ketoacyl synthase (KS)domainSequence analysis1 PublicationAdd BLAST | 457 | |
Regioni | 895 – 1216 | Malonyl-CoA:ACP transacylase (MAT) domainSequence analysis1 PublicationAdd BLAST | 322 | |
Regioni | 1206 – 1713 | Product template (PT) domainSequence analysisAdd BLAST | 508 | |
Regioni | 1281 – 1300 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 1669 – 1707 | DisorderedSequence analysisAdd BLAST | 39 | |
Regioni | 1789 – 1844 | DisorderedSequence analysisAdd BLAST | 56 | |
Regioni | 1867 – 2102 | Thioesterase/Claisen cyclase (TE/CLC) domainSequence analysisAdd BLAST | 236 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1669 – 1688 | Polar residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 1797 – 1824 | Polar residuesSequence analysisAdd BLAST | 28 |
Domaini
Family and domain databases
Gene3Di | 1.10.1200.10, 1 hit 3.10.129.110, 1 hit 3.40.366.10, 2 hits 3.40.47.10, 1 hit 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR001227, Ac_transferase_dom_sf IPR036736, ACP-like_sf IPR014043, Acyl_transferase IPR016035, Acyl_Trfase/lysoPLipase IPR014031, Ketoacyl_synth_C IPR014030, Ketoacyl_synth_N IPR016036, Malonyl_transacylase_ACP-bd IPR032821, PKS_assoc IPR020841, PKS_Beta-ketoAc_synthase_dom IPR020807, PKS_dehydratase IPR042104, PKS_dehydratase_sf IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR030918, PT_fungal_PKS IPR032088, SAT IPR001031, Thioesterase IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF00698, Acyl_transf_1, 1 hit PF16197, KAsynt_C_assoc, 1 hit PF00109, ketoacyl-synt, 1 hit PF02801, Ketoacyl-synt_C, 1 hit PF00550, PP-binding, 1 hit PF14765, PS-DH, 1 hit PF16073, SAT, 1 hit PF00975, Thioesterase, 1 hit |
SMARTi | View protein in SMART SM00827, PKS_AT, 1 hit SM00825, PKS_KS, 1 hit SM00823, PKS_PP, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit SSF52151, SSF52151, 1 hit SSF53474, SSF53474, 1 hit SSF53901, SSF53901, 1 hit SSF55048, SSF55048, 1 hit |
TIGRFAMsi | TIGR04532, PT_fungal_PKS, 1 hit |
PROSITEi | View protein in PROSITE PS50075, CARRIER, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MAQSRQLFLF GDQTADFVPK LRSLLSVQDS PILAAFLDQS HYVVRAQMLQ
60 70 80 90 100
SMNTVDHKLA RTADLRQMVQ KYVDGKLTPA FRTALVCLCQ LGCFIREYEE
110 120 130 140 150
SGNMYPQPSD SYVLGFCMGS LAAVAVSCSR SLSELLPIAV QTVLIAFRLG
160 170 180 190 200
LCALEMRDRV DGCSDDRGDP WSTIVWGLDP QQARDQIEVF CRTTNVPQTR
210 220 230 240 250
RPWISCISKN AITLSGSPST LRAFCAMPQM AQHRTAPIPI CLPAHNGALF
260 270 280 290 300
TQADITTILD TTPTTPWEQL PGQIPYISHV TGNVVQTSNY RDLIEVALSE
310 320 330 340 350
TLLEQVRLDL VETGLPRLLQ SRQVKSVTIV PFLTRMNETM SNILPDSFIS
360 370 380 390 400
TETRTDTGRA IPASGRPGAG KCKLAIVSMS GRFPESPTTE SFWDLLYKGL
410 420 430 440 450
DVCKEVPRRR WDINTHVDPS GKARNKGATK WGCWLDFSGD FDPRFFGISP
460 470 480 490 500
KEAPQMDPAQ RMALMSTYEA MERAGLVPDT TPSTQRDRIG VFHGVTSNDW
510 520 530 540 550
METNTAQNID TYFITGGNRG FIPGRINFCF EFAGPSYTND TACSSSLAAI
560 570 580 590 600
HLACNSLWRG DCDTAVAGGT NMIYTPDGHT GLDKGFFLSR TGNCKPYDDK
610 620 630 640 650
ADGYCRAEGV GTVFIKRLED ALADNDPILG VILDAKTNHS AMSESMTRPH
660 670 680 690 700
VGAQIDNMTA ALNTTGLHPN DFSYIEMHGT GTQVGDAVEM ESVLSVFAPS
710 720 730 740 750
ETARKADQPL FVGSAKANVG HGEGVSGVTS LIKVLMMMQH DTIPPHCGIK
760 770 780 790 800
PGSKINRNFP DLGARNVHIA FEPKPWPRTH TPRRVLINNF SAAGGNTALI
810 820 830 840 850
VEDAPERHWP TEKDPRSSHI VALSAHVGAS MKTNLERLHQ YLLKNPHTDL
860 870 880 890 900
AQLSYTTTAR RWHYLHRVSV TGASVEEVTR KLEMAIQNGD GVSRPKSKPK
910 920 930 940 950
ILFAFTGQGS QYATMGKQVY DAYPSFREDL EKFDRLAQSH GFPSFLHVCT
960 970 980 990 1000
SPKGDVEEMA PVVVQLAITC LQMALTNLMT SFGIRPDVTV GHSLGEFAAL
1010 1020 1030 1040 1050
YAAGVLSASD VVYLVGQRAE LLQERCQRGT HAMLAVKATP EALSQWIQDH
1060 1070 1080 1090 1100
DCEVACINGP EDTVLSGTTK NVAEVQRAMT DNGIKCTLLK LPFAFHSAQV
1110 1120 1130 1140 1150
QPILDDFEAL AQGATFAKPQ LLILSPLLRT EIHEQGVVTP SYVAQHCRHT
1160 1170 1180 1190 1200
VDMAQALRSA REKGLIDDKT LVIELGPKPL ISGMVKMTLG DKISTLPTLA
1210 1220 1230 1240 1250
PNKAIWPSLQ KILTSVYTGG WDINWKKYHA PFASSQKVVD LPSYGWDLKD
1260 1270 1280 1290 1300
YYIPYQGDWC LHRHQQDCKC AAPGHEIKTA DYQVPPESTP HRPSKLDPSK
1310 1320 1330 1340 1350
EAFPEIKTTT TLHRVVEETT KPLGATLVVE TDISRKDVNG LARGHLVDGI
1360 1370 1380 1390 1400
PLCTPSFYAD IAMQVGQYSM QRLRAGHPGA GAIDGLVDVS DMVVDKALVP
1410 1420 1430 1440 1450
HGKGPQLLRT TLTMEWPPKA AATTRSAKVK FATYFADGKL DTEHASCTVR
1460 1470 1480 1490 1500
FTSDAQLKSL RRSVSEYKTH IRQLHDGHAK GQFMRYNRKT GYKLMSSMAR
1510 1520 1530 1540 1550
FNPDYMLLDY LVLNEAENEA ASGVDFSLGS SEGTFAAHPA HVDAITQVAG
1560 1570 1580 1590 1600
FAMNANDNVD IEKQVYVNHG WDSFQIYQPL DNSKSYQVYT KMGQAKENDL
1610 1620 1630 1640 1650
VHGDVVVLDG EQIVAFFRGL TLRSVPRGAL RVVLQTTVKK ADRQLGFKTM
1660 1670 1680 1690 1700
PSPPPPTTTM PISPYKPANT QVSSQAIPAE ATHSHTPPQP KHSPVPETAG
1710 1720 1730 1740 1750
SAPAAKGVGV SNEKLDAVMR VVSEESGIAL EELTDDSNFA DMGIDSLSSM
1760 1770 1780 1790 1800
VIGSRFREDL GLDLGPEFSL FIDCTTVRAL KDFMLGSGDA GSGSNVEDPP
1810 1820 1830 1840 1850
PSATPGINPE TDWSSSASDS IFASEDHGHS SESGADTGSP PALDLKPYCR
1860 1870 1880 1890 1900
PSTSVVLQGL PMVARKTLFM LPDGGGSAFS YASLPRLKSD TAVVGLNCPY
1910 1920 1930 1940 1950
ARDPENMNCT HGAMIESFCN EIRRRQPRGP YHLGGWSSGG AFAYVVAEAL
1960 1970 1980 1990 2000
VNQGEEVHSL IIIDAPIPQA MEQLPRAFYE HCNSIGLFAT QPGASPDGST
2010 2020 2030 2040 2050
EPPSYLIPHF TAVVDVMLDY KLAPLHARRM PKVGIVWAAD TVMDERDAPK
2060 2070 2080 2090 2100
MKGMHFMIQK RTEFGPDGWD TIMPGASFDI VRADGANHFT LMQKEHVSII
SDLIDRVMA
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L42766 mRNA Translation: AAC41675.1 L42765 Genomic DNA Translation: AAC41674.1 AY371490 Genomic DNA Translation: AAS66004.1 JZEE01000728 Genomic DNA Translation: KJK60793.1 |
PIRi | T17490 |
Genome annotation databases
EnsemblFungii | KJK60793; KJK60793; P875_00052995 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L42766 mRNA Translation: AAC41675.1 L42765 Genomic DNA Translation: AAC41674.1 AY371490 Genomic DNA Translation: AAS66004.1 JZEE01000728 Genomic DNA Translation: KJK60793.1 |
PIRi | T17490 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2KR5 | NMR | - | A | 1705-1791 | [»] | |
3HRQ | X-ray | 1.80 | A/B | 1305-1660 | [»] | |
3HRR | X-ray | 1.90 | A/B | 1305-1660 | [»] | |
3ILS | X-ray | 1.70 | A | 1845-2109 | [»] | |
5KBZ | X-ray | 1.80 | A/B | 1305-1660 | [»] | |
BMRBi | Q12053 | |||||
SMRi | Q12053 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
DIPi | DIP-59286N |
STRINGi | 1403190.Q12053 |
Protein family/group databases
ESTHERi | aspor-PKSL1, Thioesterase |
Genome annotation databases
EnsemblFungii | KJK60793; KJK60793; P875_00052995 |
Enzyme and pathway databases
UniPathwayi | UPA00287 |
BRENDAi | 2.3.1.221, 523 |
Miscellaneous databases
EvolutionaryTracei | Q12053 |
Family and domain databases
Gene3Di | 1.10.1200.10, 1 hit 3.10.129.110, 1 hit 3.40.366.10, 2 hits 3.40.47.10, 1 hit 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR001227, Ac_transferase_dom_sf IPR036736, ACP-like_sf IPR014043, Acyl_transferase IPR016035, Acyl_Trfase/lysoPLipase IPR014031, Ketoacyl_synth_C IPR014030, Ketoacyl_synth_N IPR016036, Malonyl_transacylase_ACP-bd IPR032821, PKS_assoc IPR020841, PKS_Beta-ketoAc_synthase_dom IPR020807, PKS_dehydratase IPR042104, PKS_dehydratase_sf IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR030918, PT_fungal_PKS IPR032088, SAT IPR001031, Thioesterase IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF00698, Acyl_transf_1, 1 hit PF16197, KAsynt_C_assoc, 1 hit PF00109, ketoacyl-synt, 1 hit PF02801, Ketoacyl-synt_C, 1 hit PF00550, PP-binding, 1 hit PF14765, PS-DH, 1 hit PF16073, SAT, 1 hit PF00975, Thioesterase, 1 hit |
SMARTi | View protein in SMART SM00827, PKS_AT, 1 hit SM00825, PKS_KS, 1 hit SM00823, PKS_PP, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit SSF52151, SSF52151, 1 hit SSF53474, SSF53474, 1 hit SSF53901, SSF53901, 1 hit SSF55048, SSF55048, 1 hit |
TIGRFAMsi | TIGR04532, PT_fungal_PKS, 1 hit |
PROSITEi | View protein in PROSITE PS50075, CARRIER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | AFLC_ASPPU | |
Accessioni | Q12053Primary (citable) accession number: Q12053 Secondary accession number(s): A0A0F0I481, Q6UEH2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 120 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references