| IED ID | IndEnz0002013850 |
| Enzyme Type ID | protease013850 |
| Protein Name |
Hybrid PKS-NRPS synthetase pytA EC 2.3.1.- EC 6.3.2.- Pyranterreones biosynthesis cluster protein A |
| Gene Name | pytA ATEG_00913 ATETN484_0003083500 |
| Organism | Aspergillus terreus |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus subgen. Circumdati Aspergillus terreus |
| Enzyme Sequence | MPQDRFNVDAFYHPDGTHKGTTNAKYGYFLDQDLGLFDASFFNISGKEAEAMDPQQRLLLEVVYEALEDAGITLDEIQGSLTSVYCGCFTNDYNAMTAKDLEYYPKYTVTGTGNSILANRISYFYNLHGPSATVDTACSSSLVCFHLGAQSLRDAEADISIVVGSALHFDPNIFITMTDLGMLSTDGRCRHGDAAGSGYVRGEGIAAMVLKRQDRAQADGDHIRAVVRGTGVNHDGRKQGITLPSARAQADLITSTYERAGLEPAETTYVECHGTGTKAGDPRELRAVHEVFCRHRPDTLHVGSVKTNIGHLEGASGIAGLMKATMALEKKIIPPNMHFSTPNPEVDFENWKLEIPTKPKVWEMGRRTIPRRASINSFGYGGTNAHAILEEYSSSGSTTTACQQPIVSLPPDLAAMVERRPYLVPLTSHSERAGELWAGRLAQYLAKNEPSVADVALSLSTRRTMHRFRSFAVSADMEMVIERIRDPPPSAAWKSKLDTIPRIGFVFTGQGAQWFGMARSLLEQCPLFLQTIRKCDRILQALPSHRPTWSVEAELQKSQEDTMLGRTEYSQPICTAVQLALVDVLAHWGVKPSGVVGHSSGELAATYAAGLLSFENALVAAYYRGVHMGSGAAAPGSVPGAMMAVGMTEAEVTAELEPYRGRIAIAAMNSPSSFTVSGDEDAIVELQQALTDRKVFARRLQVAQAFHSHHMFPLAPGYKEALSAYPGFKANKEASAIMVSSVTGRYAGPETLGPDYLAANMTGMVKFSDALTELVLDEEDQQRIDVLLEIGPHPALKGPSNQTLDPLKLKLPYFGTLDRKQDAYESLLATTGQLFSLGYPVDLRKVNKNQFLDTTAQVVSVGAQARRLELPSYAWDHHDRYWAETRHIREHRLRPSRHSILGARVPGSLETRPRWRNYLRVSEVPWLPDHSIDGKTIFPAAGYINMVIEAAATMVDGSIREFELVDVSVKSALVVSDKDVGTETIVELAPALESAETSSSLWKQFVVLSVDEAGNQREHCTGMIRTESGSPKAIQNSSNYSSVDAFRRRSFRSTECMQYYHRLHSMGLQYGPTFQLVAGNVESGDGIAIAPISWKPTMYPREDTDLSILHPALLDACLHPVFSSIEGKLGNNLSAPYVPTFIRSLRVSGLLDAWKRSEAGFEAEVLVETDALGPRTATNDLRLHLSDGELLFDIKGLRLTSLGSNAADDTKRSLFFGTQWKPMFTGLEWAPKEEYNLTTLVELYVHQHPNSKILHVTPSLSSTESILPAFKGIADSERRNISGLVILPAGAAATDFGALVDRGNGLVSVVEDTEDAFDLVIVSTDIDMSAIRGRVADNGFLVTLNPTKTPLDTHAFHILYASSVLKIWHNKHSPNNGSVGTLTIVMPPQPTPGTRKLADIIKSQRQGPTSECDFLSLIQSSNELHGDVVVLASLDSNLYFGSALSRAEDFQAAQALLTQERQGNVIWLTRGGLMNVASPEQALILGLARSARSENPELRLVVFDIDPTADESQTAQLTSHLMDDSIREDEIAERGGRLYIPRVVASDDLNSRIPNGVRSEPTIQPLYQKDRPLALRIGRPGLLDTLMFSDDTDLTSRQLQPDDLEIEVKASALNFRDIAASMGIIDDFKLGDECAGVVLRVGSNVSSTDFAVGDRVVAWRPGQGAHRTILRNPACLCYRLQGQMPFSVASSIPLVLTTAYYSLVDTARLQRGETILIHSAAGGVGQMAIQISQNIGATIIATVGSAEKRAFLIDKYGLEDSHILSSRDDSFVEGIRRLTNGRGVDVVLNSLAGPLLLSTWASVAPFGRFVEIGKRDIHQNSRIPMDPFRRNVSFASVDMITVYERNQPLGARVFQESCALVHEGKIKPPQPITEVPYADVQRAFRMLQTGTTSGKIVLIPGPDDRVLVEQPRFHRRQLFDAHKTYLLVGGLGGLGRRLSEWLFQRGARHLAFLSRSGKSRPEARETVEWLEARGVEVKVFSGDATDSTAVNTAVSQVDGSSHRLAGVFQAAMVLQDAPLGQMTFAQWQRCMAPKIQGAYNLHNATASLPLDFFVCFSSVSAILGSKAQANYSAANSYLDALCAYRRSIGLVGTTMNVGMVVGVGAVSEDAQLQTVMERIGYDAVNEEELFAQIGAAVCPVGSQDKLALVDSQGRDAHQIITGVNLRRPTYFWANEPRFRNLYANHDFAGSSEGKNKKQDVMSQLREAPDEAARVSILTLRFLEKIASVLSVDQSTLQPNRSLGDYGLDSIVAIEIRQWFFKAVGVELAMFDILSSRSIQALIEKVASLIVLKNEAESSTAANADVQKNAKRAANRTADSTISLLPPIDGASIVEMPIMEVPMSSYQRRLWFMHNLSADPSFLNLPIIFRLRGQPHGPLIRRVLEELKRRNEILRTAYSEGEEFSQQVVMDDCTTELPAVDFSTDGDTESSLSNYVKALQQEQMDIEDGVVMKAALAKLSEDRHALVLIFHHICIDRGSSQSFLEQFTSLYDAMRKERNLASVARPAVSYGEFSVWHNTLLRSTDMQPSLAFWKSVYEDRPATAMQLLPFAKGDRPETNDYRRHVHKTTLKKTLLQRMKRICSRLGVTPAQFLMAGLRAFLYRHTEEEDLTIHLVDGNRPHPAVNDTLGFFVNVVPVRCRIDHSGSFEDVLRQIKDLVISALQHSQFPFDAIIDAVGAARTTSHFPLGQVILNYQVHGTMPVYSAGDFDITEVQGDDIPTACEIGLEALEDPAEGLKLRLEYSSTLYGEDDMARFLDNFVAFLASTIHDYRQPVSEVNMVGSKELEFLKANMFNLNFVPNTWGGMSVPERILAMAREYPQEVAVESSEGVNNLTYASLVTQASDIARAIIDSGIQPASKVGLFALPGPTAVASMVGVLFAGCGYVALDPDFAKERLAFMITDSGAKLVLAGDGLEDSACALSTVPVLASERIQHSGKMIDSPVPTEGNFPFYTIYTSGSTGTPKGVVLSQSNTQQMLSTLHHDYRFSPADRFLHHSSISFDLSVVQVFSALTTGARVCVAGAEIRKDPLALATYMAAAQVSITYFTPTQFAMLIESAGSILEGMTNYRIAYFAGERLPVRLVKAFYDLKTPAKLYNTWSPSELVVQTTIQSVAYPADDALNIPIGFPMANTRHYILDSKAKPLPMGVVGEIVVGGAQVGLGYINRPEINERAFLPDPFCSEEDHRRGWGRMFRTGDKGRFLPGGNLEFHGRIAGDKQVKLRGYRVDLSEVEHRIFVESNKGSTDVAVVDLAVVAREIAGETSQGNGTDDRQLIAFVVPRQAPPRERLSMFAFQLNQMAGKYLNPYMLPAAYQFVERLPTTIGGKVDLQRLLNCPLNLVFPVEENVNPQSPAGETSDDQDVVLKAVIQGFRQILKLPSTRAVGPGDSFFALGGNSLLLMRLQARLKRALKLPLPLNMMFKTPTPAAITQLMTGRISSSATPTVQTPATDAVDWEVETRLGDDVKPSPVNIGRSQVNSVLVTGVDSFIGVHMLATLLEDQSIDNIYVLGSQKQIQVTDIYQSFDHYHLSGLLPSREELDLRIRSVPGNLASPQFGLSAAAFRQLARNIQSIYHLGGYVSLLRSYDALQDSNVRPIHDIIHLATLGRVNTAIHHLSTWSVPHLQTWSTTTHQRGKGQPSITATEVSASHFIPESSGRLGYFKSRWAAEMILEKAAERGFAVAIYRASAVTADRRTGIPEPKDDFIRTMILSMLQTKAVPRLPARERPFVVDFVPVDYITRGMHALAMHETLNEETTEKAPIYHLSNPQPLPLEELPAIMEAIGGERGQSLPVDEWLEAVARLDTAPEAQVRWGALKEYFGLGHLMFGLDTAKTQRALKALDIGSCSPVDVEYLRTMLARESQRVG |
| Enzyme Length | 3861 |
| Uniprot Accession Number | P9WEZ4 |
| Absorption | |
| Active Site | ACT_SITE 138; /note=For beta-ketoacyl synthase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 599; /note=For malonyltransferase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 930; /note=For beta-hydroxyacyl dehydratase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 2.3.1.-; 6.3.2.- |
| Enzyme Function | FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of pyranterreones, a family of antioxidative compounds (PubMed:32077283). The first step of pyranonigrins biosynthesis is performed by the hybrid PKS-NRPS synthetase pytA that condenses 4 malonyl-CoA units ato the acetyl starter unit by the modular PKS of pytA (PubMed:32077283). The acyl chain is then connected to an L-serine through the amide bond by the modular NRPS of pytA (PubMed:32077283). A tetramic acid is formed and released from the PKS-NRPS pytA to give pyranterreone 5 with the help of the thioesterase pytI (PubMed:32077283). Pyranterreone 5 could be methylated by pytC to afford pyranterreone 6 (Probable). Both pyranterreones 5 and 6 are subsequently oxidized by the FAD-linked oxidoreductase pytB and the cytochrome P450 monooxygenase pytD to form the fused gamma-pyrone core, resulting in pyranterreones 7 and 11, respectively (PubMed:32077283). The hydroxy group at C-8 of pyranterreones 7 and 11 are dehydrated by the aspartyl protease pytH to form a delta-7 double bond to give pyranterreones 3 and 1, 2 accordingly (PubMed:32077283). The exo-methylene of pyranterreone 3 could be reduced into a pendant methyl by reductase pytE to provide pyranterreone 4, also known as cordylactam (Probable). Pyranterreone 4 can be reconverted to pyranterreone 3 through pytB-catalyzed dehydrogenation or further oxidized to pyranterreones 9 and 10 (Probable). {ECO:0000269|PubMed:32077283, ECO:0000305|PubMed:32077283}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:32077283}. |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Domain (2); Modified residue (2); Region (8) |
| Keywords | Ligase;Multifunctional enzyme;Phosphopantetheine;Phosphoprotein;Repeat;Transferase |
| Interact With | |
| Induction | INDUCTION: Expression is positively regulated by the cluster-specific transcription factor pytR. {ECO:0000269|PubMed:32077283}. |
| Subcellular Location | |
| Modified Residue | MOD_RES 2249; /note=O-(pantetheine 4'-phosphoryl)serine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00258; MOD_RES 3393; /note=O-(pantetheine 4'-phosphoryl)serine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00258 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 424,040 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |