Protein: Fatty acid synthase alpha subunit aflA (Q8TGA2)
Organism: Aspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1)
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. The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2). 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. 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
Sequence: MVIQGKRLAASSIQLLASSLDAKKLCYEYDERQAPGVTQITEEAPTEQPPLSTPPSLPQTPNISPISASKIVIDDVALSRVQIVQALVARKLKTAIAQLPTSKSIKELSGGRSSLQNELVGDIHNEFSSIPDAPEQILLRDFGDANPTVQLGKTSSAAVAKLISSKMPSDFNANAIRAHLANKWGLGPLRQTAVLLYAIASEPPSRLASSSAAEEYWDNVSSMYAESCGITLRPRQDTMNEDAMASSAIDPAVVAEFSKGHRRLGVQQFQALAEYLQIDLSGSQASQSDALVAELQQKVDLWTAEMTPEFLAGISPMLDVKKSRRYGSWWNMARQDVLAFYRRPSYSEFVDDALAFKVFLNRLCNRADEALLNMVRSLSCDAYFKQGSLPGYHAASRLLEQAITSTVADCPKARLILPAVGPHTTITKDGTIEYAEAPRQGVSGPTAYIQSLRQGASFIGLKSADVDTQSNLTDALLDAMCLALHNGISFVGKTFLVTGAGQGSIGAGVVRLLLEGGARVLVTTSREPATTSRYFQQMYDNHGAKFSELRVVPCNLASAQDCEGLIRHVYDPRGLNWDLDAILPFAAASDYSTEMHDIRGQSELGHRLMLVNVFRVLGHIVHCKRDAGVDCHPTQVLLPLSPNHGIFGGDGMYPESKLALESLFHRIRSESWSDQLSICGVRIGWTRSTGLMTAHDIIAETVEEHGIRTFSVAEMALNIAMLLTPDFVAHCEDGPLDADFTGSLGTLGSIPGFLAQLHQKVQLAAEVIRAVQAEDEHERFLSPGTKPTLQAPVAPMHPRSSLRVGYPRLPDYEQEIRPLSPRLERLQDPANAVVVVGYSELGPWGSARLRWEIESQGQWTSAGYVELAWLMNLIRHVNDESYVGWVDTQTGKPVRDGEIQALYGDHIDNHTGIRPIQSTSYNPERMEVLQEVAVEEDLPEFEVSQLTADAMRLRHGANVSIRPSGNPDACHVKLKRGAVILVPKTVPFVWGSCAGELPKGWTPAKYGIPENLIHQVDPVTLYTICCVAEAFYSAGITHPLEVFRHIHLSELGNFIGSSMGGPTKTRQLYRDVYFDHEIPSDVLQDTYLNTPAAWVNMLLLGCTGPIKTPVGACATGVESIDSGYESIMAGKTKMCLVGGYDDLQEEASYGFAQLKATVNVEEEIACGRQPSEMSRPMAESRAGFVEAHGCGVQLLCRGDIALQMGLPIYAVIASSAMAADKIGSSVPAPGQGILSFSRERARSSMISVTSRPSSRSSTSSEVSDKSSLTSITSISNPAPRAQRARSTTDMAPLRAALATWGLTIDDLDVASLHGTSTRGNDLNEPEVIETQMRHLGRTPGRPLWAICQKSVTGHPKAPAAAWMLNGCLQVLDSGLVPGNRNLDTLDEALRSASHLCFPTRTVQLREVKAFLLTSFGFGQKGGQVVGVAPKYFFATLPRPEVEGYYRKVRVRTEAGDRAYAAAVMSQAVVKIQTQNPYDEPDAPRIFLDPLARISQDPSTGQYRFRSDATPALDDDALPPPGEPTELVKGISSAWIEEKVRPHMSPGGTVGVDLVPLASFDAYKNAIFVERNYTVRERDWAEKSADVRAAYASRWCAKEAVFKCLQTHSQGAGAAMKEIEIEHGGNGAPKVKLRGAAQTAARQRGLEGVQLSISYGDDAVIAVALGLMSGAS
InterPro domains: - IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [492-729]
- IPR040899: Fatty acid synthase subunit alpha, acyl carrier domain (domain) [74-232]
- IPR008278: 4'-phosphopantetheinyl transferase domain (domain) [1549-1642]
- IPR020841: Polyketide synthase, beta-ketoacyl synthase domain (domain) [833-1428]
- IPR018201: Beta-ketoacyl synthase, active site (active_site) [1104-1120]
- IPR016039: Thiolase-like (homologous_superfamily) [794-1515]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [75-153]
- IPR047224: Fatty acid synthase subunit alpha-like, C-terminal (domain) [994-1425]
- IPR037143: 4'-phosphopantetheinyl transferase domain superfamily (homologous_superfamily) [1547-1665]
- IPR026025: Fatty acid synthase alpha subunit, yeast (family) [10-1666]
- IPR050830: Fungal fatty acid synthase (family) [25-1493]
- IPR041550: Fatty acid synthase type I, helical (domain) [259-456]
- IPR014030: Beta-ketoacyl synthase-like, N-terminal (domain) [1002-1198]
- IPR004568: Phosphopantetheine-protein transferase domain (domain) [1548-1663]
- IPR014031: Beta-ketoacyl synthase, C-terminal (domain) [1275-1382]
- IPR013968: Polyketide synthase-like, ketoreductase domain (domain) [494-569]
Interaction partners: - Fatty acid synthase beta subunit aflB
- Acyl transferase domain protein
- Malonyl-CoA:ACP transacylase (MAT) domain-containing protein
- Acyl transferase domain protein
- Acetyl-CoA carboxylase central region
- Fatty acid synthase subunit alpha
- Ketosynthase family 3 (KS3) domain-containing protein
- Beta-ketoacyl synthase C-terminal domain protein
- Eukaryotic long-chain fatty acid CoA synthetase LC-FACS
- Fatty acid synthase subunit alpha
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0016746 (acyltransferase activity), GO:0016747 (acyltransferase activity, transferring groups other than amino-acyl groups), GO:0004312 (fatty acid synthase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006083 (acetate metabolic process), GO:0046483 (heterocycle metabolic process), GO:0006082 (organic acid metabolic process), GO:1901376 (organic heteropentacyclic compound metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0045122 (aflatoxin biosynthetic process), GO:0043436 (oxoacid metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:0019752 (carboxylic acid metabolic process), GO:0043386 (mycotoxin biosynthetic process), GO:0046222 (aflatoxin metabolic process), GO:1901378 (organic heteropentacyclic compound biosynthetic process), GO:0032787 (monocarboxylic acid metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:0005829 (cytosol), GO:1902494 (catalytic complex), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm), GO:0140535 (intracellular protein-containing complex)