The following text describes a protein:
Function:
Dodecapentaenoate synthase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2). Within the pathway, the polyketide synthase af370 produces the dodecapentaenoyl group of fumagillin via the condensation of one acetyl-CoA starter unit and 5 malonyl-CoA elongation units. The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520. The multifunctional cytochrome P450 monooxygenase af510 then converts beta-trans-bergamotene into 5-keto-demethoxyfumagillol via several oxydation steps 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene. The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin. Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (Probable).
Domain:
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (By similarity); The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-ter of the protein (By similarity).
Sequence:
MTLTYGHKRLQDAPEPIAIVSAACRLPGHVNGPHKLWELLQSGGTAVSNEVPQSRFSSEGHFDGSGRPGTMKALSGMFIEDIDPAAFDAAFFNLTRADAIAMDPQQRQLLEVVYECFENGGIPIEKVRGKQIGCYVGSLNGDYHDMQMRDPEQRVSGHAVGTGRAILSNRISHFFDLRGSSFTIDTACSSGLVGVDVACKNLRAGTLTGAVVAGVNLWLSPEHTEERGTMRAAYSASGKCHTFDAKADGYCRAEAVNAVYLKRLSDAVRDGDPIRAVIRGTASNSDGWTPGINSPSAQAQAAMIREAYANAGIDSSEYAETGYLECHGTGTPAGDPTEVKGAASVLAHMRPPASPLIIGSVKSNIGHSEPGAGLSGLIKAMLVVEEGEIPGNPTFLNPNPAIDFDNLRVYATRIRIPWPKESSHYRRASVNSFGFGGSNAHAVLDNAEHYLGKYWASLEIPRSHLSSYINLSDMLSLFDGRRSSKTVTRRPQVLVFSANDMDSLKRQISTLSAHLLNPRVKVKLSDLSYTLSERRSRHFCRAFLLSYPAKSGHASKIAVEEAQFSKISQEATRIGFVFTGQGAQWSQMGLELVRTFPGVVKPILEQLDNVLQELPADLKSEWSLLQELTEARSSEHLSRPEFSQPLVTALQLAQLAVLQSWGVRAEAVIGHSSGEIAAACSAGLLTPRQAILNAYFRGLAGKSALATSPKGMMAVGLGAQDVQPYLEGVSADVVIACHNSPASVTLSGSASTLAELEGTIKAAGHFARMLRVEVAYHSPHMAKIANRYEELLKEHGRLDDGSKTNKRSNRMISTVTEDEVTGAQVCDAAYWKANMLSPVRFDGACNKLLTNTQLAPNFLIELGPSNTLAGPVTQIARAAKVDNLTYAAANKRGPDESSRAIFDVAGHLFLQNADISLDKVNLGDNTPDKAKPAVIVDLPNYQWKHSTHYWHESLASKDWRFKKFPSHDLLGSKVIGTLWQSPSWHKMLRLSDVPWLRDHRIGSEILFPAAGYLAMAMEAVRQAALSTATAEARELLKTRHYRYCLRDVQFPRGLVLEDDAEVHIMLLLVPMAKLGQGWWEYKITSLAESDSVASSSSSTLSPEKWNINSTGLVRLETILEASSSRAPEHTCSLPLDNPTPGQMWYKSLRDAGYSYGPSFQRLVAVESTEGKSATRSLISLEPPRSKWEPQSEYPLHPAPLDSVLQSMFPSLHRGNRTKLDQLLVPRGIGELTVSGDIWKSGEAISVTTWNKVSGDASLYDPASRSLIMQLNSVSFSPMLDGRDSLYMSHVYTQLTWKPDFQLLDTDEKLQQALSGGDGAASSLVQDLLDLAAHKAPNLRVLEFNLVPGSSESLWLAGHPTPRAVRTALTEFHFAANSADTALAAQEEYAEWPAARTARFSVLDPFSKALAVPAGSSQFDLVIIRRPQHADLGELDILVGNLRRLTSDGGSVIFYDSKQSSLSGGRGLANGHNHFPAALQRFGLTKVRQTRDGSCIVAEVSPAQNLSLRNDFRVVIVRFSTARSTIIDHTISQLRQFGWTLTEICIYNESGTGLPQLPPKSTVLVLDELDRPLLATATDHEWTALQAIIQSECNLLWVTEGSQVRPTAPLKAVAHGIFRTVRAEVPMMRIVTLDVESATTESLGTNASAINMALREITLADRSSLPIECEIAERGGLLHVSRIWPDAGVNKRKVEDNAGGAPPVLTNLHDSKSTIRLMASRPGSLEALHFAEQGRDVCSRQDMGPDDVEVEIFAAGCNSRDIDVAMGDISGDLDGLGLEGAGVVVRVGACVSARCVGQRVAVFGKGCFANRVTVSCKATFPLPDAMSFEQAATLPIALLTALYAVGRLAHVQGDDRVLVHSPCTDVGIACIRLCQRSGSTPFATVDNLEQRHFLTHELGLPEDHIFMSEPAAFPRALRHATKGHGLDVIISQPANRNLDNENMRLLAPGGRLIGIANGGADVGNLLPTGSLAPNCSFQRLDVTALPEKTIESVFLELSRLVTDGSVQPLSPSTLLGYEEIPKALQLLREGTHIGKIVISDPRGTKLAVLTRPATTLAQSMINPSHCYLLVGGLKGICGSLAIHLASHGAKNIAVMSRSGGGDQVSQGIARNIRALGCSLDLLQGDVTSISDVRRAFSQISVPLGGIIQGAAVFRDRTFESMSHEDYHAAVSSKVTGTCNLHTVSLETNQPISFFTMLSSISGVIGQKGQANYAGGNAFQDAFAEYRRALGLPAISIDLGPVEDVGVIHGNEDLQNRFDGSTLLSINEGLLRRIFDYSILQQHPDPQHRLNVTSQGQMITSILVPQPEDSDLLRDCRFRGLRALGEHSPRSRRDPTKDKEIQSLLFLAQSQDPDRAALRAAAITVVGARLAKQLRLTDAVDPARPLSYYGLDSLAAVELRTWVRMTLAIELTTLDVMNAASLGELCEKVIGKMGFGM