Q4WAZ9 · PSOA_ASPFU
- ProteinPKS-NRPS hybrid synthetase psoA
- GeneNRPS14
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids4007 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
PKS-NRPS hybrid synthetase; part of the gene cluster that mediates the biosynthesis of pseurotin A, a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation (PubMed:17464044, PubMed:17722120, PubMed:24082142, PubMed:24939566).
The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566).
The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566).
Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566).
The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566).
Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).
The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566).
The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566).
Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566).
The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566).
Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 182 | For beta-ketoacyl synthase activity | ||||
Sequence: C | ||||||
Active site | 321 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 364 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 1001 | Proton acceptor; for dehydratase activity | ||||
Sequence: H | ||||||
Active site | 1179 | Proton donor; for dehydratase activity | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] synthase activity | |
Molecular Function | fatty acid synthase activity | |
Molecular Function | ligase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | nonribosomal peptide biosynthetic process | |
Biological Process | pseurotin A biosynthetic process | |
Biological Process | secondary metabolic process | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePKS-NRPS hybrid synthetase psoA
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Fumigati
Accessions
- Primary accessionQ4WAZ9
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000416555 | 1-4007 | PKS-NRPS hybrid synthetase psoA | |||
Sequence: MVYTHSPKEPIAIIGTGCRFPGGSTSPSKLWDLLYSPRDLTREVPAESRFNPKGFYNVDGEHHGASNATNAYFIEEDPRYFDAGFFSIAPREAESIDPQQRLLLETVYEAMENAGLTLNGMRGSATSAYMGAMSADYTDTQLRDIENVSKYMITGTSRALLANRLSYFFDWKGPSISVDTACSSSLAAVHLGVQALRAGECTISCVGGSNIILNPDCYLAATSLHLLSPTGRSQMWDQAADGYARGEGVCVFFMKTLSQALRDGDRIDALLRETCVNSDGRTQGIALPSAEAQVSLMRTAYKNAGLDLSKAEDRPQYIEAHGTGTQAGDPREAYAIATTFFPPGEDHSHRPKLVVGSVKTIIGHTEGCAGIAGILKAVLAMRHKTIPPNQHFHNLNPSVKPSFKHLSIATSPQPWPVVPPDTPLRASVNGFGSGGTNCHAIVESYVPEIHDNGPWGKPKEMTQVPNGVAAPETDFSPIPLIFSASSGTALRAMLERYQEYLERTEVSLLRLAMTLNSHRSTLPVRVSIPGTSKADVLAAIRTQLAKVGSNPGAEIGTRSSVPEFDHVRRPKILGVFTGQGAQWAGMGQGLMAKSALFRQVIEVMEEAMAQLPDGPEWSLKEEIMKPPKTSRLGEAEISLPVCAALQVGLVKVLRSAGITFSMVVGHSGGEIGSAYAAGKISEVDAIKIAYYRGVYTKLAIGKDGKKGGMIAVGFGYEDGLNFCAMEQFADRLTVAASNSPKSVTLSGDLDAVHEAKELLDAEGVFNRVLRLDTAYHSPHMYPCAAPYLAAIERCGLVAGKSNGTAWASSVYDDNRMMTSAQDKDLEAAYWKDNLIGRVLFSQAVERALDEGNGDFDLALEIGPHPSLKGPTLETIRHKIGSEIPYSGVLDRKADDILALSTALGFSWLTLGSGVVDFAGYVSGFDPSNASILNAPALPDLPTYPWDHKKVLYRESRLNKNVRHRVDPPHPLLGSRTPDDTDYEPRWRNFLIMEELPWLRDHCVQGQIIVPAATYSVMALEAAKVLCRGKHVQSIELSDVAILRPIVLDEASDGTETLFSVRSDLDSNKKHEDEIHAQFTLSAGAMDDRHLRTAATGHIRITLAAEAPSSFPNGPRPTELDLLPTSVDRFYASMDEIGLSYSGPFRAMTSMKRRLNVASATVAVDRDLAGTIPVHPTWLDACFQTFLAAFAAPRDGSLWTAFMPTAIGRMVFSPSSTSQVPGRSVTVDAHITDFAPGYQVSLPTLTGDMSIFNSETNQLQIQIEDFVMSSFLPASEKDDRRFYLQNVWGQEMLSGALCAAAERCVAPTESESKIIDTCEKAVHYYLSKLKAAGLLDQWADKNPGLRSLMNEIEARVTSIPEQSDLVSMLGEVGEHIDLVLVRTIGESLLNSPSEGLGPITPSPMGALISRWHHEGLGFAQLQRHFVSAAKQISHQHANLRILQVGPSSPGLVRSVCQELGRSLERYTLVDDSEQTIEEMKSALAADQLRVDFTTASVENGIDAVNHLTSAGGFDLVIVHKAFTKQVTALKTVRNLLRPGGFMLMMAATGAQLRFPFMLMSTLPSLDDERLAQTKFINATRAETHDLLRQIGFSGVDSIALDNVPDKHTFSVVVSQALDDHIAFLRSPLTSPSPVPLSGNLLVVGGFSADIAKLATAIQSLVSTVWHGDIINVRTLAELDDEASTVEAVLSLTDLDRPVLEDVRAPTFRGLQRLFSEAKTVLWITHRAKADNPYHNATIGLGRSFQSENPQKVLQFLDVDTLDGVESAIAETFLKLIGGVNMRNSNPADPTRLWTIEPEVSLENGKYLVPRLFPDTERNDRLNALRRKVQTQVSVETQPISLSRSAQSDQVAYTAEAVHFHRDLADGATDPVTIQVELCSTEPVIPNIDNEDLFCFVGRTSEGARLVGLSTSNSSVVKVPREWTIPVDKHTSHDQGAFVLELRNEIQSLVIAKSIPPGSTTLIYEPDPHLAASLQRPGRPATSSVSFRARSTWSIPGSHILIDPHASRKDIQAKVPPKTRMLIHMEQGPETCEFLALRQALPPYATVVAFNDLAADDVNPRELLAEALSIIRGDSQSTKVPFDPSSVVKASALVAGGTREHANAAVVDWTGAQSITLSPRPVDTRNLFSPNKTYLLVGLTGHIGQSICRWMVQGGARHIVVTSRHPEKQGQLWREELLRQGVNIVIEAADVTKEHDLLDLRARIVSSMPPVGGIANGAMVLDDKLFIDMPFESFQAAMKPKVQGSIYLEEVFSADNLDFFLFFSSISVMTGQRTQANYVAANNFMVAMAERRRARGLPASVIDIGMVVGIGVIQRSQNDKGVSAMENSIRQMDYMPVSETDLHHLLAEAILVGQRDESPELITGLETYKPVEGEAPFWHHNVRFSHLITDPDAAQAGADSAGSAQKSLKEMLLSSGGPEEARKVMENALLQYLASSLKLSRETIYTDVPIIDLGIDSLVAVQIRNWTWAEAGYDLPVLKILGGSSVTQICDEVVASLSFDKSSIAAAKVDSQAAPAHKLRPWDKPSADTKRTDSIAPVPRSQIAANGPNGLPNGALKKASKLAVKVRPLWTTQAGGKDTKKGPRPAPIRIQPLSLGQSRLYFLSQYMDDDRVLNCTISYALSGKLDVSKLEQSLIQVVQRHEALRTSFYTDEKDGKPMQGLLEKSPFRLRVVPGVSASSDVETEFNLIRYRPYDLEQADTFAATLLSHSPDSHTLICGYHHIIMDGVSWQIFQKDLAMFYNNSGIADSAKHLPAQYSEFTRKQQEDLSCGAYAERLRFFQDQFREPVESLPLFPFAKVGTRKVVKQYAVQEATTHLNAKVVSAIKQASQTSRTTPFHFYLSAFQVLLHRLLETDKMCIGVVDANRSDQNFVNTIGFFLETIPLWFKVNSEQRFVELLKETRTKAYAALAQTGVPTEEILRACGVASSTTETPLFQVCFNYRMGAGRTAALQGVEMKFLDYVDAQNPFDLVATVDDLDDGTAMITLYLQDYLYDQEGAQLLATMYANVLQVLAENPERLVGSVSISNATLEDEGVKLGTGPILDLVAPSTPTLSKIFHTWVDKDPHALAVKDTTGKSKTYVQLAERANAIAASLLNAGAAPSIPIGVLLDPGVDTIATILAILRIGAAYVPLDTRSSDAVLSDILQESQPGIVIHHSATAPRSQILLKASAKTKLVTLNAVPQKTIRKIQDVSVPEGLAMILYTSGSTGSPKGIPLTNANIRTPILGVSERVPLGREVVLQQSGQGFDAAVYQIFIALANGGTLIMVDNRDDPAKVAALMAQESVTCTTHIVSEMQALLKYGYDELRNCSSWRIAMVAGEAFTVHLLDQFRALNRPDLKVINAYGPTEASICSSLGEVSFNRISSSETSIPIGKAIPNYGTYIVDQHCKPVPLGWPGEVAIAGPGVASGYLNLGELTQAKFRSAATLGEVFGSDCLYLTGDRGRMLSDGSIVLSGRVDGDDQVKIRGHRVQLGDVARALVQASRGVFADAAVILKGDDTSNPQLVAYVVFSRTSNIQDQQTYLRQLNQDLPVPAYMRPAITIPLDTLPVTDRGKLDSKKLASLPLPSISVDYEEDEQLTPTEARLRDVWKNVLGDIASSIPIRRSSDFFSVGGNSLILLALKAEIAQVFGVGLSVSELFQASTLELLAARLDGTSLLAQINWEEETAPDETQFTLPPPINGINGHGSSNGHAQGISVLLTGATGFLGGHILRQLVQLPSVEHVHCVAIRPNKVDVRRQLSVESPKIIRYSGDLALPNMGMSESEFSDLFKSIDVIVHNGAEVSHMKNYRSLRAANFLSTVGLARAAVSRGIPIHYISTGGVARLSVADEQPEASLAAFHPPIDGSDGYVASKWASEVFLEKVQRRFQGQVWIHRPSSITGDDVPDNDIAHSLLKFSRELGAVPELTGSGFFDFINVETVSNNIAASVVRSSEKSGGGLIYLHQSGEQVIPVGDLQKYVEELEGRPLQVLPLKEWVDLSIRKGLDEVLGSYMLASKGVIRAPLLQRGPHVE | ||||||
Modified residue | 2455 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S | ||||||
Modified residue | 3612 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Keywords
- PTM
Interaction
Protein-protein interaction databases
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-444 | Ketosynthase family 3 (KS3) | ||||
Sequence: KEPIAIIGTGCRFPGGSTSPSKLWDLLYSPRDLTREVPAESRFNPKGFYNVDGEHHGASNATNAYFIEEDPRYFDAGFFSIAPREAESIDPQQRLLLETVYEAMENAGLTLNGMRGSATSAYMGAMSADYTDTQLRDIENVSKYMITGTSRALLANRLSYFFDWKGPSISVDTACSSSLAAVHLGVQALRAGECTISCVGGSNIILNPDCYLAATSLHLLSPTGRSQMWDQAADGYARGEGVCVFFMKTLSQALRDGDRIDALLRETCVNSDGRTQGIALPSAEAQVSLMRTAYKNAGLDLSKAEDRPQYIEAHGTGTQAGDPREAYAIATTFFPPGEDHSHRPKLVVGSVKTIIGHTEGCAGIAGILKAVLAMRHKTIPPNQHFHNLNPSVKPSFKHLSIATSPQPWPVVPPDTPLRASVNGFGSGGTNCHAIVES | ||||||
Region | 575-897 | Malonyl-CoA:ACP transacylase (MAT) domain | ||||
Sequence: VFTGQGAQWAGMGQGLMAKSALFRQVIEVMEEAMAQLPDGPEWSLKEEIMKPPKTSRLGEAEISLPVCAALQVGLVKVLRSAGITFSMVVGHSGGEIGSAYAAGKISEVDAIKIAYYRGVYTKLAIGKDGKKGGMIAVGFGYEDGLNFCAMEQFADRLTVAASNSPKSVTLSGDLDAVHEAKELLDAEGVFNRVLRLDTAYHSPHMYPCAAPYLAAIERCGLVAGKSNGTAWASSVYDDNRMMTSAQDKDLEAAYWKDNLIGRVLFSQAVERALDEGNGDFDLALEIGPHPSLKGPTLETIRHKIGSEIPYSGVLDRKADDIL | ||||||
Region | 969-1105 | N-terminal hotdog fold | ||||
Sequence: HPLLGSRTPDDTDYEPRWRNFLIMEELPWLRDHCVQGQIIVPAATYSVMALEAAKVLCRGKHVQSIELSDVAILRPIVLDEASDGTETLFSVRSDLDSNKKHEDEIHAQFTLSAGAMDDRHLRTAATGHIRITLAAE | ||||||
Region | 969-1147 | Dehydratase (DH) domain | ||||
Sequence: HPLLGSRTPDDTDYEPRWRNFLIMEELPWLRDHCVQGQIIVPAATYSVMALEAAKVLCRGKHVQSIELSDVAILRPIVLDEASDGTETLFSVRSDLDSNKKHEDEIHAQFTLSAGAMDDRHLRTAATGHIRITLAAEAPSSFPNGPRPTELDLLPTSVDRFYASMDEIGLSYSGPFRAM | ||||||
Domain | 969-1276 | PKS/mFAS DH | ||||
Sequence: HPLLGSRTPDDTDYEPRWRNFLIMEELPWLRDHCVQGQIIVPAATYSVMALEAAKVLCRGKHVQSIELSDVAILRPIVLDEASDGTETLFSVRSDLDSNKKHEDEIHAQFTLSAGAMDDRHLRTAATGHIRITLAAEAPSSFPNGPRPTELDLLPTSVDRFYASMDEIGLSYSGPFRAMTSMKRRLNVASATVAVDRDLAGTIPVHPTWLDACFQTFLAAFAAPRDGSLWTAFMPTAIGRMVFSPSSTSQVPGRSVTVDAHITDFAPGYQVSLPTLTGDMSIFNSETNQLQIQIEDFVMSSFLPASEK | ||||||
Region | 1120-1276 | C-terminal hotdog fold | ||||
Sequence: DLLPTSVDRFYASMDEIGLSYSGPFRAMTSMKRRLNVASATVAVDRDLAGTIPVHPTWLDACFQTFLAAFAAPRDGSLWTAFMPTAIGRMVFSPSSTSQVPGRSVTVDAHITDFAPGYQVSLPTLTGDMSIFNSETNQLQIQIEDFVMSSFLPASEK | ||||||
Region | 2131-2305 | Ketoreductase (KR) domain | ||||
Sequence: TYLLVGLTGHIGQSICRWMVQGGARHIVVTSRHPEKQGQLWREELLRQGVNIVIEAADVTKEHDLLDLRARIVSSMPPVGGIANGAMVLDDKLFIDMPFESFQAAMKPKVQGSIYLEEVFSADNLDFFLFFSSISVMTGQRTQANYVAANNFMVAMAERRRARGLPASVIDIGMV | ||||||
Domain | 2418-2495 | Carrier 1 | ||||
Sequence: EARKVMENALLQYLASSLKLSRETIYTDVPIIDLGIDSLVAVQIRNWTWAEAGYDLPVLKILGGSSVTQICDEVVASL | ||||||
Region | 2513-2550 | Disordered | ||||
Sequence: PAHKLRPWDKPSADTKRTDSIAPVPRSQIAANGPNGLP | ||||||
Region | 2589-2885 | Condensation (C) domain | ||||
Sequence: QPLSLGQSRLYFLSQYMDDDRVLNCTISYALSGKLDVSKLEQSLIQVVQRHEALRTSFYTDEKDGKPMQGLLEKSPFRLRVVPGVSASSDVETEFNLIRYRPYDLEQADTFAATLLSHSPDSHTLICGYHHIIMDGVSWQIFQKDLAMFYNNSGIADSAKHLPAQYSEFTRKQQEDLSCGAYAERLRFFQDQFREPVESLPLFPFAKVGTRKVVKQYAVQEATTHLNAKVVSAIKQASQTSRTTPFHFYLSAFQVLLHRLLETDKMCIGVVDANRSDQNFVNTIGFFLETIPLWFKV | ||||||
Region | 3076-3478 | Adenylation (A) domain | ||||
Sequence: TYVQLAERANAIAASLLNAGAAPSIPIGVLLDPGVDTIATILAILRIGAAYVPLDTRSSDAVLSDILQESQPGIVIHHSATAPRSQILLKASAKTKLVTLNAVPQKTIRKIQDVSVPEGLAMILYTSGSTGSPKGIPLTNANIRTPILGVSERVPLGREVVLQQSGQGFDAAVYQIFIALANGGTLIMVDNRDDPAKVAALMAQESVTCTTHIVSEMQALLKYGYDELRNCSSWRIAMVAGEAFTVHLLDQFRALNRPDLKVINAYGPTEASICSSLGEVSFNRISSSETSIPIGKAIPNYGTYIVDQHCKPVPLGWPGEVAIAGPGVASGYLNLGELTQAKFRSAATLGEVFGSDCLYLTGDRGRMLSDGSIVLSGRVDGDDQVKIRGHRVQLGDVARALVQ | ||||||
Domain | 3576-3652 | Carrier 2 | ||||
Sequence: TPTEARLRDVWKNVLGDIASSIPIRRSSDFFSVGGNSLILLALKAEIAQVFGVGLSVSELFQASTLELLAARLDGTS | ||||||
Region | 3696-3920 | Reductase (R) domain | ||||
Sequence: LTGATGFLGGHILRQLVQLPSVEHVHCVAIRPNKVDVRRQLSVESPKIIRYSGDLALPNMGMSESEFSDLFKSIDVIVHNGAEVSHMKNYRSLRAANFLSTVGLARAAVSRGIPIHYISTGGVARLSVADEQPEASLAAFHPPIDGSDGYVASKWASEVFLEKVQRRFQGQVWIHRPSSITGDDVPDNDIAHSLLKFSRELGAVPELTGSGFFDFINVETVSNNI |
Domain
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (PubMed:17464044).
Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:17464044).
Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase (PubMed:17464044).
NRPS14 contains also a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a dehydratase domain (DH), and 2 ketoreductase domains (KR) (PubMed:17464044).
NRPS14 has the following architecture: KS-AT-DH-KR-T-C-A-T-KR (PubMed:17464044).
Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:17464044).
Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase (PubMed:17464044).
NRPS14 contains also a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a dehydratase domain (DH), and 2 ketoreductase domains (KR) (PubMed:17464044).
NRPS14 has the following architecture: KS-AT-DH-KR-T-C-A-T-KR (PubMed:17464044).
Sequence similarities
In the C-terminal section; belongs to the NRP synthetase family.
Keywords
- Domain