Protein: Hybrid PKS-NRPS synthetase iliA (PKS-NRPS iliA) (EC 2.3.1.-) (EC 6.3.2.-) (Ilicicolin H biosynthesis cluster protein A) (P0DO30)
Organism: Neonectria sp. (strain DH2)
Function: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2-pyridonealkaloid that has potent and broad antifungal activities by inhibiting the mitochondrial respiration chain. IliA assembles the backbone of ilicicolin H. The PKS portion and trans-acting enoyl reductase iliB work together to construct an octaketide, and two methyl groups are introduced by the MT domain during the chain assembly. The nascent chain is then condensed with tyrosine, catalyzed by the C domain, and the resulting PKS-NRPS hybrid is offloaded by the RED domain to form an advanced tetramic acid intermediate. The biosynthesis of ilicicolin H starts with formation of the tetramic acid by the hybrid PKS-NRPS synthetase iliA with the partnering trans-enoyl reductase iliB since iliA lacks a designated enoylreductase (ER) domain. The cytochrome P450 monooxygenase iliC then catalyzes the ring expansion of the tetramate to the acyclic 2-pyridone. The pericyclase iliD further converts the acyclic 2-pyridone into 8-epi-ilicicolin H. 8-epi-ilicicolin H might then spontaneously convert to ilicicolin H, since ilicicolin H is produced in the absence of the epimerase iliE, in contrast to what was observed for the Talaromyces variabilis ilicolin H biosynthetic pathway (Probable).
Interaction partners:
Sequence:
MSQQRYPEPIAVIGSACRFPGASSSPSKLWSLLQEPRDVLKKFDPDRLNLKRFHHTNGDTHGATDVNNKSYLLEENTRLFDASFFGISPLEAAGMDPQQRLLLETVYESFEAAGVTLDQLKGSLTSVHVGVMTNDYSFIQLRDPETLSKYNATGTANSIMSNRISYVFDLKGPSETIDTACSSSLVALHHAAQGLLSGDCETAVVAGVNLIFDPSPYITESKLHMLSPDSQSRMWDKSANGYARGEGAAALLLKPLSRALRDGDHIEGIVRGTGVNSDGQSSGITMPFAPAQSALIRQTYLRAGLDPIKDRPQYFECHGTGTPAGDPVEARAISESLLDGETSSDNPLYVGSVKTVIGHLEGCAGLAGVIRAILALKHRTIPPNLHFKELNPAIAQYYGPLQITTKALPWPEVPAGTPARASVNSFGFGGTNAHAIIESYDNGSASSSIQAQDEQPEESSEGGLGPLIFSAASGSSLLRTVQAYLEHLREHPSVDLQDLSWLLQTRRTTHRVRTHFSGASRDTVLENMATFVTTHEKASSATIGYQPQLVNPSEAPGVLGIFTGQGAQWPAMGRELIQKSPLFRKTIEECEAILNALPEGDVPEWSLMQELTADASSSRLSEAMISQPLCTAVQLGLVNLLTAAGISFDAVVGHSSGEIAATYASGIITTKGAMQIAYYRGFHAKLATGPDGERGGMLAAGLSFEKATQFCSRPEFQGRIQVAASNAPQSVTLSGDINAIKEAKEQLDADNIFARQLKVDTAYHSHHMQPCAGPYLQSLLACDIELQAPKPGSCVWNSSVRGDAELLKRDLSSLKGTYWVANMVQTVLFSQAIESSIWHGGPFDLAIEVGPHPALKGPVEQTLKAAYGSVPMYTGALKRNGSDVEAFSAALGVTWAQLGPSFVDFSSFREAFYESQAPAPKVIKDLPTYSWDHEKDYWRESRISRRYRTGKDVGHELLGRRTPDDNDHELRWRNVLKLSEMPWVRGHEVLDEVLLPGAAYVSIAVEAGKHLATSTGKSVRLIDVENVDILRPVVVPDNQEGVETLFTAHILSSSPSEGVLRARFSYYICNDQSSGSMVHTCSGDLVVHLGADSESGDLLPPRDAVPPNLVNIDGERVYKMFEGIDLKYSGVFRSIADSKRCLNYATATGVWPEGSLSNDYGVHPAMLDVAFQTLFIARAHPASRQITSALLPSHIDRVRVSPSVQILQPEGGGDIKAAFESWVVGQTATSLTGDLNVYDAETGKTFLQVEGLATNMVGEQDASHDQPIFSKTVWGRYDSVGLADPVRDAVKDAEATRLAEDIERVALFYIKRIVNQIGADERAGFQWYHQRMFGAFEKHLATIKNDEHPVLPSNWLADEPSVLEDISNAHPDSIDLQLLHAVGENLADVVRGDTQLLEVMQEDDMLDRFYMDNCASAPINQSIADVLQQITFKFPRCNILEIGAGTGGTTWSVLNSINNAYDSYTYTDISSGFFPNAAEKFSDFSNKMAFKILDVEKDPTTQGFVEESYDVIIAANVLHATRSLETTLRNVRSLLKPGGFLVLMEVTGMQSVRVTFILGGLPGWWLGADDGRPLGPGVSVVDWDVLFDKTGFSGADTVMHDLEDDTKHCNSLIVTQAVDDAFLRMREPLSFMAELPPLTEPLLVIGGKKLTTTKMMSEIQKLLPRSWKRHVQTVGSIDEIDTAKLIPRMDVICLQEADEPLFATPMTAKRIALLKSLLMSARNMLWVTGAGKSHTPRTSIFLGIARIVPSELPQLNLQMLGLESGASHSVAARNCVEAFLRLRATEEGNGSHMLWSQEPEMEILADGQTMVPRVMPNKPLNELYNASRRAVTKTIDATDVPVRAVAGPGKMTLQAAELQDASAQRARVQVKYALHIPSVNGKQVYLVCGHRQGSESATPVMAISESNGTIVEVDLERLITIDEDGCTPGVLAATANHLLVRAIATLASGARKVLLYQAEESLAAMVATEIAAQGGEAHFASSSSDAPDSWIKIHVNSSKRALSRVVPRDVQLYVDCSGYSQSAVSSVSSASDTLRACVPADCVAQQLGGGLLQEAFQRMDAGGSTLFKDSYAKAKSSFSENQEQILDCDLVKAADLAGADASSLTRKRYVTDWQEKESLTLTIQPLDLQGIFKPDKTYFMVGMAGGLGLSICQWMIRNGAKHLVITSRNPKIDDSLLEDARRANAKLHVMTMDVSKRDSVEKVVRLVQDTLPPIAGVCNAAMVLSDKLFIDMDVDQLNNTLAAKVYGTEHLDSVFDDMPLDFFVLLSSVATVIGNIGQANYHAANLFMTSLIAQRRARGLTGSVVHVGYISDVGYVTRQDRDRQLDQHFRNVRLMPLSETDVHHAFAEAIRGGKPGSVSGAHDIIMGLETFKEPLAPEKQPLWLANPRFAHFMPPTMLQTQQQHRGSGSADNVRKQVEEAETEDEAVAAVVKAFCSKLESILQLQEDSVNIQRAIIDLGIDSLVAVEIRTWFLKELGAEVAVVKILGGDTVIQVCTWATKKVMAINMKKKEAAQLDEAAAEKTATAATPAPAPDAAPAPAAPTKTASLTVPVENTSRTPESNSASVSDADDSESSGAVSKLGTSISGSSYAKMEFGDADARSESTGSSGMADSDDSSNRPETIREEIMSQAQSRIWFLSKHLEDPAAFNMTFHYRAQGPLSMARLRHALQVTTHHHECLRMRFYPRLGDGQPMQGVMGSSLYELEHIPDANDSDVKNELARFKTRVWDLENGKTFGVTVLSHSAEEHDIIYGYHHLVMDVVGWHVFVHDLDKAYKMQSLDKSAGSYFDYTSLQLEQEKAGVLEEDLKYWQAEFTTTPETLPLLPMAHTIVRPAEPGNESHHEYQELTSGQFTALKETCQRLRISPFHFHVAVMQVLLARYANTEDVCIGIVDANRNDARFAQTVGCFINMLPVRSHVSSHDSFANVARAASKKALAAFAHSAVPFDMILDKVKAPRSSASTPLFQAAVNYRTGSVWELPLGDCQMKLAGAKDADNPYDISLGITDMGSGCMIEIHCQASLYTSEGCRTILDSYVRLLESFAANPHLDITECEIYDKSQVGQALELGKGPEMEFGWPSTMSQRVLDMCSLHSDKSAVKDNTITLSYSNLASRVNAVADAILQAGCTAGSHVAVLCEPTVDATVAMLAVLHVGAVYVPLDTSLPTARHAAMVQSSRPALLLSHSATEGLVRDLGNELDSPIRQVRIDSISEEARQEVPCAAERGAPAVLLFTSGSTGTPKGIFLSQANFVNHLALKIHVLGFGQECVLQQSSLGFDMSLIQTFCALANGGLLVIVPSEMRRDPVELTGLLSRERISLTIATPSEYLAWLRYGEASLTENTAWRHACMGGEQVSRQLKSELRRVNLSGLRLTNCYGPTEITAAATFQAIDLEEKQDEDERAKFAVGKALPNYSVCILDASGQPQPAQHAGEICIGGAGVALGYLNLADETARKFIADVTSTADRRMYRTGDQGRLLSDGTLLCLGRLDGDTQVKLRGLRIELQEVESALLQAADGLLSTAVVSQRGDVLVAHATLSPGRDNASEEELTQVLGHLRLPQYFIPAAIIILAAMPTNSNGKLDRKAIGALSLPERGSNGTQEKMTIREGEVRLLWERVLPDTSTTGRLAPSSDFFLCGGNSLLMMKLQAAIRESIGVAISTRTLYQASTLREMARRIDEHQTAEGDDTEREIDWAAETTVPKALLRQIRELPAPVKSSKSDGIEVLMTGATSFLGGHLLQALLRSPVVRKVHCVAVLADDQHQLPRDEKIECYTGSLLSSTLGLNADERDRLEQTVDVIIHAGSSGHCLNTYDSLRTPNLLSTHFLSSLALPRSIPLLLLSSNRVVLLSGSTAPPPGSVAAFAPATDGLEGYTASKWASESFLENLVAHMQQVSRSPLTVAVHRPCVVVSEQAPNSDALNAILRYSVSMRCVPQLDNVEGYLDFGKVEKIVDEIADSALQLAQAGSQDQEIRFRHHSGGAKVPVREFRAHMEDIYGGSFDEVDVTEWMRRAADAGIDPLITAYLEGILDSGSPMVFPYLGEE