Q30DW5 · PKSA_DOTSE

Function

function

Polyketide synthase; part of the fragmented gene cluster that mediates the biosynthesis of dothistromin (DOTH), a polyketide toxin very similar in structure to the aflatoxin precursor, versicolorin B (PubMed:12039746, PubMed:17683963, PubMed:22069571, PubMed:23207690, PubMed:23448391).
The first step of the pathway is the conversion of acetate to norsolorinic acid (NOR) and requires the fatty acid synthase subunits hexA and hexB, as well as the polyketide synthase pksA (PubMed:16649078, PubMed:23207690).
PksA combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor NOR (By similarity).
The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase hexA/hexB (By similarity).
The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase nor1, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin (PubMed:23207690).
The cytochrome P450 monooxygenase avnA then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN) (PubMed:23207690).
The next step is performed by adhA that transforms HAVN to averufin (AVF) (PubMed:23207690).
Averufin might then be converted to hydroxyversicolorone by cypX and avfA (PubMed:23207690).
Hydroxyversicolorone is further converted versiconal hemiacetal acetate (VHA) by moxY (PubMed:23207690).
VHA is then the substrate for the versiconal hemiacetal acetate esterase est1 to yield versiconal (VAL) (PubMed:23207690).
Versicolorin B synthase vbsA then converts VAL to versicolorin B (VERB) by closing the bisfuran ring (PubMed:16649078, PubMed:23207690).
Then, the activity of the versicolorin B desaturase verB leads to versicolorin A (VERA) (PubMed:23207690).
DotB, a predicted chloroperoxidase, may perform epoxidation of the A-ring of VERA (PubMed:23207690).
Alternatively, a cytochrome P450, such as cypX or avnA could catalyze this step (PubMed:23207690).
It is also possible that another, uncharacterized, cytochrome P450 enzyme is responsible for this step (PubMed:23207690).
Opening of the epoxide could potentially be achieved by the epoxide hydrolase epoA (PubMed:23207690).
However, epoA seems not to be required for DOTH biosynthesis, but other epoxide hydrolases may have the ability to complement this hydrolysis (PubMed:23207690).
Alternatively, opening of the epoxide ring could be achieved non-enzymatically (PubMed:23207690).
The next step is the deoxygenation of ring A to yield the 5,8-dihydroxyanthraquinone which is most likely catalyzed by the NADPH dehydrogenase encoded by ver1 (PubMed:23207690).
The last stages of DOTH biosynthesis are proposed to involve hydroxylation of the bisfuran (PubMed:23207690).
OrdB and norB might have oxidative roles here (PubMed:23207690).
An alternative possibility is that cytochrome P450 monoogenases such as avnA and cypX might perform these steps in addition to previously proposed steps (PubMed:23207690).

Cofactor

pantetheine 4'-phosphate (UniProtKB | Rhea| CHEBI:47942 )

Note: Binds 1 phosphopantetheine covalently.

Pathway

Mycotoxin biosynthesis.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site544For beta-ketoacyl synthase activity
Active site679For beta-ketoacyl synthase activity
Active site722For beta-ketoacyl synthase activity
Active site995For acyl/malonyl transferase activity
Active site1372Proton acceptor; for dehydratase activity
Active site1570Proton donor; for dehydratase activity
Active site2234For thioesterase activity

GO annotations

AspectTerm
Molecular Functionfatty acid synthase activity
Molecular Functionnorsolorinate anthrone synthase activity
Molecular Functionphosphopantetheine binding
Biological Processfatty acid biosynthetic process
Biological Processtoxin biosynthetic process

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Norsolorinic acid synthase
  • EC number
  • Short names
    NSAS
  • Alternative names
    • Dothistromin biosynthesis polyketide synthase
    • Polyketide synthase A

Gene names

    • Name
      pksA

Organism names

Accessions

  • Primary accession
    Q30DW5

Phenotypes & Variants

Disruption phenotype

Impairs the production of dothistromin but still enables the conversion of exogenous aflatoxin precursors, including norsolorinic acid, into dothistromin (PubMed:16649078).

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004434561-2399Norsolorinic acid synthase
Modified residue1770O-(pantetheine 4'-phosphoryl)serine
Modified residue1911O-(pantetheine 4'-phosphoryl)serine
Modified residue2057O-(pantetheine 4'-phosphoryl)serine

Keywords

Expression

Induction

Expression is positively regulated by the dothistromin-specific transcription factors aflR and aflJ (PubMed:23207690, PubMed:25986547).
Dothistromin biosynthetic proteins are co-regulated, showing a high level of expression at ealy exponential phase with a subsequent decline in older cultures (PubMed:17683963, PubMed:18262779).

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region10-247Starter unit:ACP transacylase (SAT) domain
Domain372-805Ketosynthase family 3 (KS3)
Region905-1192Malonyl-CoA:ACP transacylase (MAT) domain
Region1307-1327Disordered
Region1340-1483N-terminal hotdog fold
Domain1340-1658PKS/mFAS DH
Region1353-1658Product template (PT) domain
Region1510-1658C-terminal hotdog fold
Region1665-1734Disordered
Compositional bias1711-1726Pro residues
Domain1733-1812Carrier 1
Domain1877-1953Carrier 2
Domain2020-2099Carrier 3
Compositional bias2098-2122Polar residues
Region2098-2149Disordered
Region2164-2393Thioesterase/Claisen cyclase (TE/CLC) domain

Domain

The domain architecture includes starter unit:ACP transacylase (SAT), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), product template (PT), 3 acyl-carrier domain (ACP), and thioesterase/Claisen cyclase (TE/CLC) domains (PubMed:16649078).
Although duplicated ACP domains are common, pksA is the only fungal PKS containing 3 ACP domains (PubMed:16649078).
The third (C-terminal) ACP is less similar in sequence to the first two and to that of the aflatoxin biosynthetic enzyme aflC (PubMed:16649078).
It is possible that the third ACP domain was acquired by unequal recombination and has since diverged into a slightly different form that may have less functionality or altered specificity (PubMed:16649078).

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,399
  • Mass (Da)
    259,252
  • Last updated
    2005-12-06 v1
  • Checksum
    C82F86A242F2AFE4
MTHSNATRVLVFGDQTYDFVPKLRELFHVKDNPILTAFLEQSHYVVRAQMIQTLPPAEHKAARTFDLADMLKKYVAGKLNPAFQTALSCITQLGVFMREFHDFTKPYPRHDSSYVLGICTGSLAAAAVSSSNSLSELLPIAVQTALIAFRLGLCVTDMRDRLESSEEDRTQPWSVVLFDTDEQTVTKAIKDFCTSNVLPKTKQPWITSASSKTITISGAPRVLKKLSQEPALKDKKTRQIPIYVPAHNSALFTPEDVKSILETTPVDTWSNYPTKLPFISSVSGKMAWADNYLAVIHLALNQCLLESIGWGKVETELPRLLKSRGAENVLITPITTSADRALSAALSPTISNIEVEKPTINESFAHRPGSGKSKLAIVSMSGRFPEAQSTDAFWDLLYKGLDVVKEVPKRRWDVETHVDPTGRARNKGATKWGCWLDFAGEFDPRFFSISPKEAPQMDPAQRMALMSTWEAMERGGIVPDTTPSTQRNRIGVFHGVTSNDWMETNTAQNIDTYFITGGNRGFIPGRINFCFEFSGPSFTNDTACSSSLAAIHLACNSLWRGDCDTAVAGGTNMIFTPDGHAGLDKGFFLSRTGNCKPFDDKADGYCRAEGVGTVMVKRLEDALADGDPILGTILDAKTNHSAMSDSMTRPFVPAQIDNMEACLSTAGVDPTSLDYIEMHGTGTQVGDAVEMESVLSVFAPNEQFRGKDQPLYVGSAKANIGHGEGVSGVTSLIKVLLMMQNNTIPPHCGIKPGSKINHNYPDLAARNVHIAFEPKPFLRREGKLRRVLINNFSAAGGNTALLIEDAPDRMPLSGQDPRTTQTVTISGHVGKSLSNNVANLLAHLKKNPTIDLSQLAYTVSARRWHHLHRVAVAGTTVADITAKLEKAIENKEGVNRPKAKPSVFFAFTGQGSQYLGMGKQLYDSYPMFRSELQGYDRLAQSQGFPSFAHIFTETKGDVEQNLPVVVQLAITCLQMALFNLVTSFGIKASAVVGHSLGEYAALYAAGVLSASDTIYLVGKRAELLQDHCQRGTHAMLACKASEWSLAEITAGKNVEVACVNGPEDTVLSGTVEEIGEVQKTLSAKSIKATLLKLPFAFHSAQVQPILEDFEELAAGATFEKPKLAVISPLLGSVVEDEGVVGPNYLARHCREAVGMVKALGVAKEKGIINEKTIVIEIGPKPLLCGMIKNILGQNIVALPTLKDKGPDVWQNLSNIFTTLYTGGLDINWTAFHAPFEPAKKVLQLPDYGWDLKDYFIQYEGDWVLHRHKIHCNCADAGKDVHNTSHYCPGKHTFAENVVVPGGAQKAVQEAPAAKTETKKMSKLDPTKEAYPGIPLTTTVHKVIEEKTEPLGAQFTVETDISRKDVNSIAQGHTVDSIPLCTPSFYADIALQVGKYAMDRIRAGHPGAGAIDGRVDVTDLVVDKALIPHGKAPQLLRTNVTMSWPPKMAATTRSAKVTFKTYTADGKLDTDHAYCTVRFTTDSQQKSLQKKVPEYKAAIAKLRARDAKGELTHYNTKSGYKLMSSMAHFHPDYKLLDNLVLNEAENEAVSVMNFSSCTDAGIYAAHPAYVDAITQVGGFAMNAKDDTDIDKEVYVNHGWESFQVYKKMEKSVEYVVYSKMTKDPKGDMVHGDTIVLDGDEVVAFFRGLSLRSVPRKALRAVLQSAMDKGIRQRGGKPGAAKGAVAAPAPAKKMVEPVKAASKKETPAAAAPPSPSKAAPPPAPKPAALKASVPKADPGKVDEALKIISEESGIALDELTDDSNFTDMGVDSLSSMVITSRLREDLELDLAPDFALFADCPTVASLRTFLAGAAGGPTDSPAAIATLEFGEPTPAKELEAGPALKSTPISPGVQALQPVPAPTPAPKPVITSPAAPVSSKVFDDALQIISEESGIALDELTDDSNFTDMGVDSLSSMVITSRLREDLELDLSPDWALFADCPTVASLRSFLGGSGPGSTAPADADTPVDTTAAEIEAPVPNEAASYMPNSSQADVDDAVAAVIGNDPPRRPEPPKQAAAPAVARTEALNAALDIIAEESGVAAEDFTDDTIFSDIGIDSLCSMVISSRFREELELDLDSQFSLFVDLPTVAQLREFLTGSSADSDSSSVASNPADPAATPPRSESSDTEPDDEAPSKPKSGPGSTDSCRSTNSVILQGKPKTAAKTLFLLPDGGGSASSYSVIPKLQSDVAVVGINCPYARDPENMTCTWQAMMQSFINEIKRRQPKGPYHLGGWSSGGAFAYVTAEKMIKQGDEVGSLFIFDAPVPQVMEKLPREFYEAVNFTESTAVGTAEPPPYLIPHFMAVVDVMLDYKCKPLQTKKMPNVGLIWADSTVMKEDEAPKMKGMHFMIQKRTNFGPDGWDEVCPGAKFEIVKAVDTNHFTLMTKARVNYVSDLIDKVMG

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1711-1726Pro residues
Compositional bias2098-2122Polar residues

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ149246
EMBL· GenBank· DDBJ
AAZ95017.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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