| IED ID | IndEnz0005000534 |
| Enzyme Type ID | lipase000534 |
| Protein Name |
Non-reducing polyketide synthase ausA EC 2.3.1.- Austinoid biosynthesis clusters protein A Methylorcinaldehyde synthase ausA |
| Gene Name | ausA AN8383 |
| Organism | Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus subgen. Nidulantes Emericella nidulans (Aspergillus nidulans) Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) |
| Enzyme Sequence | MGSLDDNTLQQVSVLFGPKYPEVELPAGHIRRYLSNQRNANWLHDAIRDLPSVWHDILRLWPAAEKLHGDARLRQLSAFLGGGTLRPDMAEPMNFLLVPATVLRHLVDFLELKEDKNYDVCDIQGFCVGFLAAIAAACWSDNEDEFGKVVSTVLRLAVYIGAAVDLDELCEQPARSIAVRWRTAQEHKLLTEVLTRYQGAYISCVTDENAVTVTVWDSQSVSFAKELEKHGLSVKTTTLRGRFHHSNHTQAVEDILQSCERNSRLCLPSKCHKRSLPRSNINGRVCEADSLFTVAVESILTTQANWKITVTATLDNMGQSDARSIIPIGAGQFVPRHARCRMLNIVEFNKGEHINGRRKMQSATALDVGVNVTAPETTAVPIAVTGMACRYPQADSVEELWRILDLGQCTVSPMPNSRLKSGSLQREPKGPFFGNYLARPDAFDHRFFGISAREAESMDPQQRVLLQVAYEAMESAGYCGLRRSKLPDDIGCYVGVGCDDYSENVGSRNATAFSATGTLQAFNSGRISHYFGWSGPSVTVDTACSSAAVAIHLACQAIRTNDCAIAVAGGVNIMTDPRWSQNLAGASFLSPTGASKAFDADANGYCRGEGAGLLVLRPLEAALRDGDPIHAVITGTSVNQGANCSPITVPDSNSQRSLYLKALSLSGLTPDVVGYVEAHGTGTQVGDPIEFESIRKTFSGPNRATKLYVGSIKDNIGHTETSSGVAGMLKTILMIQKRRIPKQANFRRLNPRITLNERNHIEIPTQSIDWEAEKRVAMVTNYGAAGSNAAIVLREPASTPATSNSAHRETLPSHVPFYVSARTEESLRSYCEALQSTIREVAQSGTNTVQHIAYNLARKQNRDMEHFVTFPAAAGEPSELMTRLGSIASAHTQVERRSQSFHPVIICFGGQTGDTASISRNLFESCELLRFHVDECENACNALDLPSLFPAIVSPFPNKDIVNLHCVLFSIQYATAKAWLDSGLQVTRMIGHSFGQLTALCVAGGLSLIDGMRLVATRAQLIQKHWGPHTGVMLSLRASKEKVQALLDAASGHADLACLNGPDNFVVAGDEESIRRIEIIATEKGMHVELKRLKNTHAFHSRLVDAILPGLSEVANTLTFRQLDIPVEACAEQEDDWLWVTGDKIVQHSRKPVFFHDAVERTLSRVDGPCVWLEAGTASPVINMVRRVVEASRPLKSHVYLPTDLSGAQAQANLAKVTCTLWSKAVPVQFWPFHPSETGYRWINLPPYQFAKTSHWIEYNPDAFRSPPQVPDQENVQEASLVRLLRQDGKEALFTINNKDNVFRMCTAGHAVANQNLCPASLYFELVVQAALLVSSTATKPTMYHIESLNICSPLVLGMPGAVLLQLTQQDESHGQWSFVLSTRDGLQDAVTHATGRVSLQAAGSNTGICARLSSLQRLLNLASWNSIATSPSSSGLKRSTVYQAFARAVNYADYYRGVEEVYAVGHEATGRVILPSSPTKCNPCDPILIDNFIQVAGIHVNCLSETHDDEVFVCSSVGDVLIGESFVRRDTAATVPWAVYSNYEPESKKKIVCDVFVLDHTTGALAVCMLSATFTGVSIQSLKRTLNRLSNHTARPTEAEQVSINVAAEATALSSTPVAHVSSSDGDLLAVQTMLGELLGISADELSAAAALGDIGVDSLMSTEVLTEINKRFGVAISNAELTQIPDVGGLVQRIFPGHSVVRIKTHSQGAVETEITITDREPKSISVDLAPVCDTSPTAFVDKASKLFATTRTSAEFSRKTRFAGFCDTVFPQQMELVTSYVVEAFHALGADLASLTPGQVVPPVKILPQHGKVMNQLVAVLEYSDLIERRESEIIRSQQPVGTVPSLILYKKILNKHAQHASEHKLLHTTGSRLAECLSGKADPLSLLFQNAEARALMTDVYSNAPMFKSATIQLAQYLKDLLFNLGTQREIKVLEIGAGTGGTTNYLVQELAAVPGLRFQYTFTDISSSLVTLARKRFKAYDFMRYTTLDIENDPSPELQGQYDIIISTNCIHATRNLITSCTNIRRLLRPEGILCLIELTRNLFWFDLVFGLLEGWWLFNDGRSHALAHERLWDHNLRQAGFNWVDWTDNDSAESDILRLIVASSTQPFYALEGDDECEADCNTVQEQTVLYNTRDGLELFADIYYPEKTDRSGAKRPIALLIHGGGHIMLSRKEIHHEQVRMLFDMGFLPVSIDYRLCPEVSLLDGPMQDACDALAWARNKLPQLQLQRRDILPDGNNVVAVGWSTGGHLAMTLAWTAPARGVSAPEAILSFYSPTDYTDPFWSKPNFPYRVDVSTSDIQTGNPLDALQDAPISGYNPPPSKRALGGWMAPSDPRSRIALYMNWTGQTLPVLFYGCNYRARAAESGQDYEVVLPEPILSEVQKVCPFSQISAGSYRAPTFLIHGTLDDLIPVQQAQRTHDKMQACGVDSDLRIVRDGLHLFDLEANFAGNQHAFQAVVDGYEFLRRHVGL |
| Enzyme Length | 2476 |
| Uniprot Accession Number | Q5ATJ7 |
| Absorption | |
| Active Site | ACT_SITE 544; /note=For beta-ketoacyl synthase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 993; /note=For acyl/malonyl transferase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 2251; /note=For thioesterase activity; /evidence=ECO:0000269|PubMed:23368695; ACT_SITE 2413; /note=For thioesterase activity; /evidence=ECO:0000269|PubMed:23368695; ACT_SITE 2445; /note=For thioesterase activity; /evidence=ECO:0000269|PubMed:23368695 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=acetyl-CoA + 3 malonyl-CoA + 2 S-adenosyl-L-methionine = 3,5-dimethylorsellinate + 3 CO2 + 4 CoA + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:49628, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:131856; Evidence={ECO:0000305|PubMed:21658102, ECO:0000305|PubMed:22329759};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49629; Evidence={ECO:0000305|PubMed:21658102, ECO:0000305|PubMed:22329759}; |
| DNA Binding | |
| EC Number | 2.3.1.- |
| Enzyme Function | FUNCTION: Non-reducing polyketide synthase; part of the gene cluster A that mediates the biosynthesis of austinol and dehydroaustinol, two fungal meroterpenoids (PubMed:22329759). The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:22329759). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (PubMed:22329759). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (PubMed:22329759, PubMed:23865690). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (PubMed:22329759). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (PubMed:22329759). Finally, the cytochrome P450 monooxygenase ausG modifies austinolide to austinol (PubMed:22329759). Austinol can be further modified to dehydroaustinol which forms a diffusible complex with diorcinol that initiates conidiation (PubMed:22234162, PubMed:22329759). Due to genetic rearrangements of the clusters and the subsequent loss of some enzymes, the end products of the Emericella nidulans austinoid biosynthesis clusters are austinol and dehydroaustinol, even if additional enzymes, such as the O-acetyltransferase ausQ and the cytochrome P450 monooxygenase ausR are still functional (PubMed:29076725). {ECO:0000269|PubMed:22234162, ECO:0000269|PubMed:22329759, ECO:0000269|PubMed:23865690, ECO:0000269|PubMed:29076725}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis. {ECO:0000269|PubMed:21658102, ECO:0000269|PubMed:22329759}. |
| nucleotide Binding | |
| Features | Active site (5); Chain (1); Domain (1); Modified residue (1); Mutagenesis (4); Region (6) |
| Keywords | Methyltransferase;Multifunctional enzyme;Phosphopantetheine;Phosphoprotein;Reference proteome;Transferase |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | MOD_RES 1660; /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 | 271,827 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:49628; RHEA:49629 |
| Cross Reference Brenda |