Q8TGA2 · AFLA_ASPPU

Function

function

Fatty acid synthase alpha subunit; 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, PubMed:15094053, PubMed:16256699).
The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741).
Within the aflatoxin pathway, the fungal fatty acid synthase aflA/aflB provides the hexanoyl starter unit to the acyl-carrier protein (ACP) domain of the norsolorinic acid synthase to allow the first step of the pathway (PubMed:15006741, PubMed:16256699).
The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. 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. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). 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. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). 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. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). 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. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). 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. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively. 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).

Catalytic activity

Pathway

Mycotoxin biosynthesis; aflatoxin biosynthesis.

Features

Showing features for active site, binding site.

TypeIDPosition(s)Description
Active site1113For beta-ketoacyl synthase activity
Active site1313For beta-ketoacyl synthase activity
Active site1354For beta-ketoacyl synthase activity
Binding site1552Mg2+ (UniProtKB | ChEBI)
Binding site1552-1554acetyl-CoA (UniProtKB | ChEBI)
Binding site1598-1608acetyl-CoA (UniProtKB | ChEBI)
Binding site1622-1625acetyl-CoA (UniProtKB | ChEBI)
Binding site1652-1654acetyl-CoA (UniProtKB | ChEBI)
Binding site1653Mg2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentfatty acid synthase complex
Cellular Componenttransferase complex
Molecular Function3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity
Molecular Function3-oxoacyl-[acyl-carrier-protein] synthase activity
Molecular Functionfatty acid synthase activity
Molecular Functionfatty-acyl-CoA synthase activity
Molecular Functionholo-[acyl-carrier-protein] synthase activity
Molecular Functionmagnesium ion binding
Biological Processaflatoxin biosynthetic process
Biological Processlong-chain fatty acid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Fatty acid synthase alpha subunit aflA
  • EC number

Including 2 domains:

  • Recommended name
    3-oxoacyl-[acyl-carrier-protein] reductase
  • EC number
  • Alternative names
    • Beta-ketoacyl reductase
  • Recommended name
    3-oxoacyl-[acyl-carrier-protein] synthase
  • EC number
  • Alternative names
    • Aflatoxin biosynthesis protein A

Gene names

    • Name
      aflA
    • Synonyms
      fas-2
      , fas-2A, hexA
    • ORF names
      P875_00052994

Organism names

Accessions

  • Primary accession
    Q8TGA2
  • Secondary accessions
    • A0A0F0HZ47

Proteomes

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004383361-1671Fatty acid synthase alpha subunit aflA
Modified residue113O-(pantetheine 4'-phosphoryl)serine

Post-translational modification

4'-phosphopantetheine is transferred from CoA to a specific serine of the acyl carrier domain by the C-terminal PPT domain. This modification is essential for activity because fatty acids are bound in thioester linkage to the sulfhydryl of the prosthetic group.

Keywords

Interaction

Subunit

[Alpha6beta6] hexamers of two multifunctional subunits (alpha and beta).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region40-60Disordered
Domain75-153Carrier
Region492-729Ketoreductase (KR) domain
Domain926-1428Ketosynthase family 3 (KS3)
Compositional bias1244-1283Polar residues
Region1244-1288Disordered
Region1497-1521Disordered

Sequence similarities

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,671
  • Mass (Da)
    181,275
  • Last updated
    2002-06-01 v1
  • Checksum
    266034C51A556FFE
MVIQGKRLAASSIQLLASSLDAKKLCYEYDERQAPGVTQITEEAPTEQPPLSTPPSLPQTPNISPISASKIVIDDVALSRVQIVQALVARKLKTAIAQLPTSKSIKELSGGRSSLQNELVGDIHNEFSSIPDAPEQILLRDFGDANPTVQLGKTSSAAVAKLISSKMPSDFNANAIRAHLANKWGLGPLRQTAVLLYAIASEPPSRLASSSAAEEYWDNVSSMYAESCGITLRPRQDTMNEDAMASSAIDPAVVAEFSKGHRRLGVQQFQALAEYLQIDLSGSQASQSDALVAELQQKVDLWTAEMTPEFLAGISPMLDVKKSRRYGSWWNMARQDVLAFYRRPSYSEFVDDALAFKVFLNRLCNRADEALLNMVRSLSCDAYFKQGSLPGYHAASRLLEQAITSTVADCPKARLILPAVGPHTTITKDGTIEYAEAPRQGVSGPTAYIQSLRQGASFIGLKSADVDTQSNLTDALLDAMCLALHNGISFVGKTFLVTGAGQGSIGAGVVRLLLEGGARVLVTTSREPATTSRYFQQMYDNHGAKFSELRVVPCNLASAQDCEGLIRHVYDPRGLNWDLDAILPFAAASDYSTEMHDIRGQSELGHRLMLVNVFRVLGHIVHCKRDAGVDCHPTQVLLPLSPNHGIFGGDGMYPESKLALESLFHRIRSESWSDQLSICGVRIGWTRSTGLMTAHDIIAETVEEHGIRTFSVAEMALNIAMLLTPDFVAHCEDGPLDADFTGSLGTLGSIPGFLAQLHQKVQLAAEVIRAVQAEDEHERFLSPGTKPTLQAPVAPMHPRSSLRVGYPRLPDYEQEIRPLSPRLERLQDPANAVVVVGYSELGPWGSARLRWEIESQGQWTSAGYVELAWLMNLIRHVNDESYVGWVDTQTGKPVRDGEIQALYGDHIDNHTGIRPIQSTSYNPERMEVLQEVAVEEDLPEFEVSQLTADAMRLRHGANVSIRPSGNPDACHVKLKRGAVILVPKTVPFVWGSCAGELPKGWTPAKYGIPENLIHQVDPVTLYTICCVAEAFYSAGITHPLEVFRHIHLSELGNFIGSSMGGPTKTRQLYRDVYFDHEIPSDVLQDTYLNTPAAWVNMLLLGCTGPIKTPVGACATGVESIDSGYESIMAGKTKMCLVGGYDDLQEEASYGFAQLKATVNVEEEIACGRQPSEMSRPMAESRAGFVEAHGCGVQLLCRGDIALQMGLPIYAVIASSAMAADKIGSSVPAPGQGILSFSRERARSSMISVTSRPSSRSSTSSEVSDKSSLTSITSISNPAPRAQRARSTTDMAPLRAALATWGLTIDDLDVASLHGTSTRGNDLNEPEVIETQMRHLGRTPGRPLWAICQKSVTGHPKAPAAAWMLNGCLQVLDSGLVPGNRNLDTLDEALRSASHLCFPTRTVQLREVKAFLLTSFGFGQKGGQVVGVAPKYFFATLPRPEVEGYYRKVRVRTEAGDRAYAAAVMSQAVVKIQTQNPYDEPDAPRIFLDPLARISQDPSTGQYRFRSDATPALDDDALPPPGEPTELVKGISSAWIEEKVRPHMSPGGTVGVDLVPLASFDAYKNAIFVERNYTVRERDWAEKSADVRAAYASRWCAKEAVFKCLQTHSQGAGAAMKEIEIEHGGNGAPKVKLRGAAQTAARQRGLEGVQLSISYGDDAVIAVALGLMSGAS

Sequence caution

The sequence KJK60794.1 differs from that shown. Reason: Erroneous gene model prediction

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1244-1283Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF391094
EMBL· GenBank· DDBJ
AAL99898.1
EMBL· GenBank· DDBJ
Genomic DNA
AY371490
EMBL· GenBank· DDBJ
AAS66002.1
EMBL· GenBank· DDBJ
Genomic DNA
JZEE01000728
EMBL· GenBank· DDBJ
KJK60794.1
EMBL· GenBank· DDBJ
Genomic DNA Sequence problems.

Similar Proteins

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