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Protein

Versicolorin B synthase

Gene

aflK

Organism
Aspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Versicolorin B 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: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: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:8662689, PubMed:15932995, PubMed:1731640, PubMed:8368837, PubMed:8784203, PubMed:14602595, PubMed:15006741). 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 cytodhrome 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).1 Publication21 Publications

Catalytic activityi

Versiconal = versicolorin B + H2O.4 Publications
5'-oxoaverantin = (1'S,5'S)-averufin + H2O.4 Publications

Cofactori

FADBy similarity

Kineticsi

  1. KM=20 µM for 5'-oxoaverantin2 Publications
  2. KM=3.1 µM for versiconal (at pH 6.0 and 30 degrees Celsius)2 Publications
  1. Vmax=6.67 nmol/min/mg enzyme with 5'-oxoaverantin as substrate2 Publications
  2. Vmax=0.15 µmol/min/mg enzyme with versiconal (at pH 6.0 and 30 degrees Celsius) as substrate2 Publications

pH dependencei

Optimum pH is 5.5.2 Publications

Pathwayi: aflatoxin biosynthesis

This protein is involved in the pathway aflatoxin biosynthesis, which is part of Mycotoxin biosynthesis.1 Publication1 Publication
View all proteins of this organism that are known to be involved in the pathway aflatoxin biosynthesis and in Mycotoxin biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei613FAD; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi84 – 85FADBy similarity2
Nucleotide bindingi105 – 106FADBy similarity2
Nucleotide bindingi171 – 174FADBy similarity4
Nucleotide bindingi624 – 625FADBy similarity2

GO - Molecular functioni

GO - Biological processi

  • aflatoxin biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-14040.
BRENDAi4.2.1.142. 523.
4.2.1.143. 523.
UniPathwayiUPA00287.

Protein family/group databases

CAZyiAA3. Auxiliary Activities 3.

Names & Taxonomyi

Protein namesi
Recommended name:
Versicolorin B synthase1 Publication (EC:4.2.1.1434 Publications)
Alternative name(s):
5'-oxoaverantin cyclase1 Publication (EC:4.2.1.1424 Publications)
Aflatoxin biosynthesis protein K1 Publication
Gene namesi
Name:aflK1 Publication
Synonyms:vbs1 Publication
ORF Names:P875_00052980
OrganismiAspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1)
Taxonomic identifieri1403190 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaeAspergillus
Proteomesi
  • UP000033540 Componenti: Unassembled WGS sequence

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00004241631 – 411 PublicationAdd BLAST41
ChainiPRO_000042416422 – 643Versicolorin B synthaseAdd BLAST622

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi116N-linked (GlcNAc...)Sequence analysis1
Glycosylationi221N-linked (GlcNAc...)Sequence analysis1
Glycosylationi507N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Interactioni

Subunit structurei

Homodimer.4 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Structurei

3D structure databases

ProteinModelPortaliQ12062.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GMC oxidoreductase family.Curated

Phylogenomic databases

KOiK17646.

Family and domain databases

Gene3Di3.50.50.60. 3 hits.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR012132. GMC_OxRdtase.
IPR000172. GMC_OxRdtase_N.
IPR007867. GMC_OxRtase_C.
[Graphical view]
PfamiPF05199. GMC_oxred_C. 1 hit.
PF00732. GMC_oxred_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000137. Alcohol_oxidase. 1 hit.
SUPFAMiSSF51905. SSF51905. 2 hits.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q12062-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRNWFQVTA MAVVPVVGIM AAVNPTILSS AASSLPSLGA MFTSDDFASQ
60 70 80 90 100
MDGRIQAQGL LSSHFGMYGW PGQSFDYVIV GGGTAGLAMA RRLSQDGTAS
110 120 130 140 150
VAVIEAGGFY ETDAGNATEV PMYLFNYFFD NGKVKNPLFD WYQYTTPQPG
160 170 180 190 200
LAQREMFYMQ GKTLGGSTAR GAMLYHRGSK GAYDMWADHV GDDSYRWDKW
210 220 230 240 250
LPYFQKSVHF SGPETNPRPA NATALNDNTA FTASGGPVHV GYPFQVNAIS
260 270 280 290 300
SWVDRALAKM GFPEAQGFSN GNLLGRSYIT HTINPYTRRR ETASSSYLRE
310 320 330 340 350
ALMESNNLNI FTRTLVKRVL FDDQNRATGV TVNTDGFEWQ IGARKEVILS
360 370 380 390 400
AGVMRSPQLL MVSGIGPKDH LEQLGIPVRS DLSGVGQNMQ DTIILGPTVP
410 420 430 440 450
VKVESHSQLM GNKETLPRAI REYNEQRKGL LTNPGQDYFA FEKHQPGMLK
460 470 480 490 500
ESTAADIDAA FPDDWPTFSY IALDDTFVPQ YDGKNYFSMS AALMTPFSRG
510 520 530 540 550
TVTINSNDTA NPPIVDPQWL ADPRDQEMAV AAFRRCREIV ASDVMREVVA
560 570 580 590 600
GPEILPGPQY QTDEEILNYI AETSDAYYAG VGTCAMGKAD DPKAVVDSKA
610 620 630 640
RVLGVKGLRI VDASIFPFAI DGQPMGTVYA LAEKIAAEMM AGQ
Length:643
Mass (Da):70,271
Last modified:November 1, 1996 - v1
Checksum:i4B903BA6A0F39D11
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51327 Genomic DNA. Translation: AAC49318.1.
U51328 mRNA. Translation: AAC49319.1.
AY371490 Genomic DNA. Translation: AAS66012.1.
JZEE01000729 Genomic DNA. Translation: KJK60751.1.

Genome annotation databases

KEGGiag:AAC49318.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51327 Genomic DNA. Translation: AAC49318.1.
U51328 mRNA. Translation: AAC49319.1.
AY371490 Genomic DNA. Translation: AAS66012.1.
JZEE01000729 Genomic DNA. Translation: KJK60751.1.

3D structure databases

ProteinModelPortaliQ12062.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

CAZyiAA3. Auxiliary Activities 3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

KEGGiag:AAC49318.

Phylogenomic databases

KOiK17646.

Enzyme and pathway databases

UniPathwayiUPA00287.
BioCyciMetaCyc:MONOMER-14040.
BRENDAi4.2.1.142. 523.
4.2.1.143. 523.

Family and domain databases

Gene3Di3.50.50.60. 3 hits.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR012132. GMC_OxRdtase.
IPR000172. GMC_OxRdtase_N.
IPR007867. GMC_OxRtase_C.
[Graphical view]
PfamiPF05199. GMC_oxred_C. 1 hit.
PF00732. GMC_oxred_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000137. Alcohol_oxidase. 1 hit.
SUPFAMiSSF51905. SSF51905. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiAFLK_ASPPU
AccessioniPrimary (citable) accession number: Q12062
Secondary accession number(s): A0A0F0I0N8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 16, 2013
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.