Detail Information for IndEnz0010001819
IED ID IndEnz0010001819
Enzyme Type ID esterase001819
Protein Name Hybrid PKS-NRPS synthetase traA
EC 2.3.1.-
EC 6.3.2.-
Terrestric acid biosynthesis cluster protein A
Gene Name traA
Organism Penicillium crustosum (Blue mold fungus)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Penicillium Penicillium crustosum (Blue mold fungus)
Enzyme Sequence MVLPQPEPIAIVGSGCRFPGSSSSPSSLWDLLEKPRDVSKEPTNERFELRGYYHPNGAHHGTMNVQRAYMLDEDVGTFDATFFNISPNEAESIDPQQRLLMEVVYEALEAGGHRLDILRGSDTAVYVGTMSVDYNDIMLRDINSIPTYFSTGTSRAILANRISYFFDWHGPSMTIDTACSSSMVALHQSVQALRSGESRVAIAGGTELLLGPEQFVGESKMNLLSPTGQSRMWDASANGYARGDGIAAIVLKKLSDAIADGDHIECLIRQTGINQDGKSTGLTVPSSAAQADLIRSTYTKGGLDIDNPRDWPQFFEAHGTGTKAGDPREASAISQCFGSQPIHGNPLYVGSIKTIIGHTEGTAGLAGVFKASLAIQHGIIPPNMLLHQLNDEVAQYCDNLRVPNAPTAWPKLPDGVPRRASVNSFGFGGTNGHAILEEYQPPTETRNTATTGRDENNASVFRIFPFSAASEESLTANLRAYATSLKTRTTVDLVDLAWTLQSRRSALPFKTSLTAECIEGLITKIDSTLEKAKANSGLKVGTRSAPTKPKVLGIFTGQGAQWATMAAGLIRTSETVRRKIEQLDGSLATLPEANRPTWRIADQLCADAEDSRLNEAALSQPLCTAIQVVLIDLLRSSGITFEAVVGHSSGEIAAAYAADYISAHDAIRIAYYRGVYAKHARGPKDQKGAMMAVGTTWEDAEELLNLPAFRGRVKIAAQNSAASLTLSGDVEALSHAKRVFDEEKKFTRLLVVDTAYHSHHMLLCSERYIHSLRTCGIQVNYNRNTSCTWYSSVKHGEPMHPEPSLGDLYWNDNMVNTVLFADAVKGAAKGSQLNLAIEVGPHPALKGPALQTLSDFEMSLPYTGVLKRKGNDLEAFSDALGFVWTHCGPGAVDFQTYEELIYPACKTPSLAIGLPAYQWDHKRVYWYQSRLAKKTQTRGEAFHELLGVPSPNNTDRDLRWSNFLKTNEIPWLNGHQLQGQTVFPAAGYVAMALEAGLKLAQGRSVKVLQIDDLTIDKAVTFDDGANFAVETLVALTGVTQGQSRTKKQTADFAVYSCANTGSSTELGVVSRGKVTVIYGTPSFSTLHSSPHNEKNMVDIQAEQFYSSLHELGYGYNGPFKTLSSTKRTLNQASARVETYGYGEDENTLIVHPTMLDVAFQASFLARMSPGDDQLWSLHVPTFIKCIRVNPELCASIPSSPTSLSLSAVLHESDSLSMLSSVDVFTEDGQETMIQVEGLSMKPFSPATADDDRSMFSTTVYGSMSPDLAMDVGNGRPPSEGLAFSQCNVALACVAQQIVHRYPHAKILEIGAGEGHATRAVLESIGSKLSYTFTDSSTEVIEKAAESFKDFKEKVLLKTFDPLGKPSSQGLDEHAYDLVIASNILASNSVSHTELENIRRLLKPGGYLLASGLTGDAPTRTLGGGTVEGNDARKHGPVNTAQWHGALRKAGFSGIDSITPQTSGMASPFSAIVTQAVDKRINFLRKPLSTPSFVRLDELVIVGNQSLKAAQLTEEIYDHLIQFCGKITVLDGLPTDDDDISSMATFINLADIHEPIFRDISAEQFEGLKCLFELASNILWVTEGARADEPYHNASIGFGRSIAYEMPHLSLQFLDLNDTGSTASRVISEAVLRLVALREWEETEHNFKDKTLWSREPELYVEKERLMVPRLLQVDDQNDRINSLRRVVTKMVDPDNSSVLISKAVDGSFVLREEVLRQSGQNFVQIKHSVLSAINVAPEAFLFLGAGFSQVTDEVVITLSDANASMSTPLAHVPAQWHTGGLSTLISAVARQLLARRLISMVVAHSHLLVHGLDENESFVSILKQHAGLKDIDIKFSAANPAANSEWIQVTPWTSSHVTRQSIPATTTHFLDLSADDKNQDAAVIIREALPVICKHIGVSDLFRPESFVPAGSKDSILRALQDAVREAKTTASSEIPSASIRPTELIDATVLKSPLSVVDWTVDGEVPVQVQPIDATQLFSQHKTYVLVGLSGRLGQSISQWMSQNGAGCICLTSRTPKADPEWQAEMEKKGTTVKLIPMDVTNRADVERVFADLRANSPPIAGVASGAAVFHDATFSEMTHEILEKVMNPKVVGTKNLDEVLGDTKLDFFIVFSSLTSVVGNSGQSNYTAANAYMTGLVGQRRKRGLAATSLDIGSIVGIGYLERASDTAREQLIRNGFMAVSETDLHQLLAEAIRAGATNSSASPMVTTGCRNVQEGEEFPVPWIDDPRMQHKVILGEHSSKAEMAGKKSALPVRDQLAVSKSTADALEILKELSECFAAKLAMISRLADGQVGHDIPLVELGIDSLVAVEVRGWFLKELKTDIPVLKVLGGGTVATLCQQALEKLPESILPNVESGGPSKTGSSKPTAKPSVAKPRSPPSPSGSETGSPGRWSENNTTSPQSTLSSDQSPSSTPATVLSNVPSNVDLTTVAKSEMALIPSSDFVKTELVSFQQSRFWFLGLLIDDQATFNVTFYLRITGNLRTGDLERAVRLVTNRHESLRTCFVAHEQEADLAYQKVLPNSLVRLKRKNINRVEDVDIEYAAMKQVPFDLASGNLMRLVLLTLSASEHYLLFNYHHILMDGVSLQNFLADLEKAYQRQPLGPPPCQVPEFSRVQRAAFESGVFNEDIAYWKNEFPNGHPVLPLLPMSHITSRMALNSFNVHQVECRVDSELMAKVREAARVNGCTTFHFYLATFKAMLFRFTDAGDLTIGIADANRISPDVEGTIGLLLNLLTLRFQRNPSQTFAQSVGEARGKALEALKHSNVPFDILLKELNVPRSSAYSPFFQAFFDYRQGHQEKLSFGSTEFEFLQVHPGRTAYDMTLDVTDGADSARILFRTQASLYDKTAAQLLLNTFIHLLDTFATNTSLKLDDFALFSDKELKLALNVGHGPNFESSWPGGTIPHRIDQIAKENDDKVALKDGHGTILTYGAMINRTQAIAAALQQVGVGESSRVLVFEDATVDWPCSMLAIMRLGAVYVPLDLRNPLPRLADVAGSCKPVAILVDSTTLDHVAQVNVTFAEVVNVSEVGVNSIKVANVSRSDAVAALLYTSGSTGKPKGIVVTHSGLRNEIEGYTSQWVLKAERVLQQSAFTFNHSSDQIYTGLVNGGFVYIVPWDKRGDPIEVTKIIKEENITYTKATPAEYSLWLDYGSGNLKQASSWRFAFGGGESLTGTITRSLATLQLPNLRFFNSYGPTEISISSTKMEVAYRDSPPDGRIPCGFMLPNYAAYILDDQRKPVPVGMPGELYIGGAGVSLGYLDNEELTEQHFLPNPYAIPEYVAQGWTRMYRTGDIAHLQGDGAMVFHNRIAGDTQVKIRGLRIELGDIESNIIKAAEGALKEVAVTLRDGDPPILVAHVVFAPHHHIVDTEAFLVQLLKNLDVPQYMVPVMAIPLERMPLSNHSKTDRKALKELPLPQRSNHDTGDNTESLTETMLELRRLWVDVLNTGELGLDIGPSTSFFTVGGNSLLIVRLQSRIRQTFNVTVRLFDLIDANTLSDMTQKIEESLNVDLIDWDKETALLSDFTMPEATKHQPLKTTDKVILVTGSGGFLGKHILTELIARPDVSKIHCIGLRDKPGNTPRRLALNSTKIITHSGDLTEPWLGLGEEKFASLTLEVDVILHMAATRSFWDNYSLLRPINVTPTKLLVQMATGRKIPIHYVSSAGVVSAEGVEILAGSAAKYQPRVDGSNGYVASRWASEQILEHAVSALDVPVSIHRFVPAKEPANQTVVVDALQHFVSFVDELSIMPDFSGTTGHFEMTPIHSAASQLAENLVKTPTQQSSLLEFVHHDCPIRIDIAEMVAFLEEQRGGKGLEKVPGLKFVGDMKRAGLAYFVTSQTLLMGGTNGTSVVLESRR
Enzyme Length 3856
Uniprot Accession Number A0A481WNP4
Absorption
Active Site
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 tra gene cluster that produces terrestric acid (PubMed:30811183). The clavatol biosynthesis cluster cla and the terrestric acid cluster tra are both involved in the production of peniphenones and penilactones (PubMed:30811183). The non-reducing PKS claF is responsible for the formation of clavatol from successive condensations of 3 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit, and 2 methylation steps (PubMed:30811183). The esterase claE probably collaborates with claF by catalyzing the hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled intermediates (By similarity). The clavatol oxidase claD then converts clavatol to hydroxyclavatol (PubMed:30811183). Spontaneous dehydration of hydroxyclavatol leads to the accumulation of the highly active ortho-quinone methide (PubMed:30811183, PubMed:31860310). On the other hand, the PKS-NRPS hybrid traA is involved in the formation of crustosic acid, with the help of traB and traD (PubMed:30811183). The polyketide synthase module (PKS) of traA is responsible for the synthesis of the polyketide backbone via the condensation of an acetyl-CoA starter unit with 3 malonyl-CoA units (PubMed:30811183). The downstream nonribosomal peptide synthetase (NRPS) module then amidates the carboxyl end of the polyketide with L-malic acid (PubMed:30811183). Because traA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase traG (By similarity). Crustosic acid undergoes decarboxylation and isomerization to the terrestric acid, catalyzed by the 2-oxoglutarate-dependent dioxygenase traH (PubMed:30811183). Both acids are further converted to the 2 gamma-butyrolactones (R)-5-methyltetronic acid and (S)-5-carboxylmethyltetronic acid, with involvement of the cytochrome P450 monooxygenase claJ (PubMed:30811183). Spontaneous addition of the methide to these gamma-butyrolactones leads to peniphenone D and penilactone D, which undergo again stereospecific attacking by methide to give penilactones A and B (PubMed:30811183, PubMed:31860310). {ECO:0000250|UniProtKB:A0A0E0RXA7, ECO:0000250|UniProtKB:A0A161CKG1, ECO:0000269|PubMed:30811183, ECO:0000269|PubMed:31860310}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:30811183}.
nucleotide Binding
Features Chain (1); Domain (2); Modified residue (2); Region (8)
Keywords Ligase;Methyltransferase;Multifunctional enzyme;Oxidoreductase;Phosphopantetheine;Phosphoprotein;Repeat;Transferase
Interact With
Induction
Subcellular Location
Modified Residue MOD_RES 2307; /note=O-(pantetheine 4'-phosphoryl)serine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00258; MOD_RES 3467; /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 420,817
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda