Protein: Hybrid PKS-NRPS synthetase iccA (PKS-NRPS iccA) (EC 2.3.1.-) (EC 6.3.2.-) (Ilicicolin H biosynthesis cluster protein A) (A0A482N9V7)
Organism: Talaromyces variabilis (Penicillium variabile)
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. IccA assembles the backbone of ilicicolin H. The PKS portion and trans-acting enoyl reductase iccB 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 iccA with the partnering trans-enoyl reductase iccB since iccA lacks a designated enoylreductase (ER) domain. The cytochrome P450 monooxygenase iccC then catalyzes the ring expansion of the tetramate to the acyclic 2-pyridone. The pericyclase iccD further converts the acyclic 2-pyridone into 8-epi-ilicicolin H. Finally, the epimerase iccE converts 8-epi-ilicicolin H into ilicicolin H via epimerization. IccA to iccE are sufficient for ilicicolin H biosynthesis and the roles of the remaining enzymes, iccF, iccG and iccH within the pathway have still to be determined (Probable).
Interaction partners:
Sequence:
MAANDSNNQTKPQLPEEPVAIVGSSCRFPGSSNSPSKLWDLLRQPRDVLKEFDPDRLNLKRFYHPDGDTHGSTDVTNKSYLLEEDSRLFDASFFTINPAEAAGMDPQQRILLETVYEAFESAGMTLEQLRGSLTAVHVGTMTNDYAGIQLRDLETIAKYNATGTANSIVSNRISYVFDLKGPSETIDTACSSSLVALHHAARGLLNGDCETAVVAGVNLIYDAASYIAESKLHMLSPDSQSRMWDKSANGYARGEGAAALLLKPLSRALRDGDHIEGVIRATGVNSDGQSPGITMPFAPTQAALIRQTYRRAGLDPVKDRPQYFECHGTGTPAGDPVEARAISEAFEPSADNPIYVGSIKTIIGHLEGCAGLAGVMKVILALKNRTIPPNMLFNELNPAIAPFYGPLQIPKKAMPWPELPENTPIRASVNSFGFGGTNAHVIIESFESSTPSSDSEKCEEGALGPLLFSAGSGASLLHTVQAYVQYLDQNPSVDLRDLSWLLQTRRSTHRVRTHFSGTSSDAILESMIKFVNNNEKTPSTEVGHQPKLINPKEVPGILGVFTGQGAQWPQMGKELIGKSPIFRRTLEDCDATLQALPSSDIPKWSLVKELMANASSSRVAEAAISQPLCTAVQLGLVNMLKASGLNFDAVVGHSSGEIAATYASGIINLQAAIQIAYYRGFHAKLAKGEKGQQGGMLAAGLTLDKAKQLCLREEFVGRLQVAASNAPQTVTLSGDLDAIEEVKKYLDEENVFARQLKVDTAYHSHHMKPCAEPYLKSLLACDIEVRKPTPGQCIWNSSVRGDTGLLKGDLSSLKGPYWVANMVQTVLFSQAVESSIWHGGPWDLAIEVGPHPALKGPTEQTLKAVYGVVPLYTGVLKRGASDVEAFSTAIGVTWSQLGPSFVDFAGYRKTFYESEPPTPKVIKDLPGYSWDHDKVYWRESRISKRYRTGRDQTHELLGRRTPDDNEFELRWRNVLKLSEMPWLRGHEVLEEVLLPGAAYVSIAVEASKHIATSKGKSIELLEVEDVDIQRPVVVPDNKEGVETLFTARLLPGSSSDKVLKALFSYYICNDQSTGTMVHTCSGRLSVHLGEAKEDVLPQRDPVPQNLVNINTDRAYGMFKDIGLNYTGVFRSIKESSRTLQYSAATGIWPEGSLSDKYLVHPAMLDVAFQTLFIARAHPASRLITSALLPSHIERIQVSPSVPILHARENSDEIKADFDCWVVHQTASSLTGDLNIYDKVSGKTFLQVEGLTTKMVGEQDASGDRPVFTKTVWGSDGSLGLDEPERDPVGDAEGLSLAEAAERMALFYMKRVVKEISPEERTKFQWYHQRMFEAFEQHLVNVGSGSHPMLKSEWLSDDSSIMDGLDRIHPTSIDLKLLRACGENMPDVVREKTQLLEVMSKDDMLNRFYMDNCAARINNDIAKVVKQISFKFPRANILEIGAGTGGTTWSILKDINDAYDSYTFTDISSGFFPKAAEKFSDFAHKMIFKTLDVEKQPSEQGFAENSYDVIVAANVLHATRSLETTLRNARSLLRPGGYLILMEITNPESLRTTFIFGGFSGWWLSEEPHRKLGPVVTAMDWDTVLNDTGYSGADMVVHDLAEESKHLTSLIVSQAVDDDFLRLREPLSNLADMSAPTESILVIGGKKLLTSKMVNEINKLLPKSWKRHISSAGSIDDIDINELKPGTEVISLQELDDPLFSTPMTAERMSTIQNLMMSAKTLLWVTTAGKSHAPRASMFHGIARIVPSELQHLQIQVLGLEAGSTPAIATRHCVEAFLRLRGTSDTTREMLWAIEPEVEIMADGQVLIPRVVPDETLNQTYNASRRVVTKTVDATDLAVEAVAGPTKMMLQTAELQAGERKTRIQVKYALHLPAMDGKGIYVVYGQRQDDTSSFVLAVSKSNSSIVDVDSKHAVSVSDNCEPATLNVLATYLIARAIATLSKQAGSVLLSEPEESLAAIVATETAKQGTQAYFLSSKKVSPVEWIKVHANASKRAIQKAVPHDVQLLIDCSGIEASGNAVMASMPLHCVERQLDAHLLFDALESTESKPESLLEEAYQYATQLITQEQVQSECEVFPASDLPLTNMLSLVHKKYVTDWQQRDSLVVSVPPLDLEGIFKADKTYLMVGAAGGLGLSICEWMIRNGAKNLIITSRKPQVDQNMIEEASRVGATVKVMAMDVSSKESVAEVVQQAQEIMPPIAGVCNAAMVLSDKMFLDMDVDQLNGTLAAKVYGTEHLDAVFADAPLDFFIVLSSTATTIGNIGQANYHVANLFMTSLVAQRRARGLAGSVIHIGYVADVGYVTRQDRERQLEQHFRNVRLMALSETDVHHAFAEAVRGGRPGNTVGSPDIIMGLEPASVPLEPERQTLWLSNPCFGHLVPSTLQNDSSQTGGTGNGSSVRRQVEEAQTEDEAVDAVLDGFCAKLEAILQLREGSVKENVQRAVIDLGIDSLVAVEIRTWFLKELGAEVPVVKILGGDTVLQICTTAAKKVMANAMKKKEEDAVAEEGGREAASKKEPAPAASAPTPAPVAPSLLDVPARAFEPDSATISEVGDDSAFSNKGSSSSATGASSPKELSDSESVPDTSKDQSHVRPETVRDERMSPAQARIWFLTKHLDDPSAYNMVFHYRVKGPLKTVRLRHALQVATGHHESLRTLFYSRLEDGQPMQGVMPASAYELKHVPGADEADLKKELALLKAREWDLENGRTFSVSVLSRAADEHDVVFGYHHIIMDVVGWYFFVRDLDRAYRMQPFDKKISGSYVDYSVMQLSQKNTAAASDDLAFWQKEFSTVPDPIPLLPIAAVSARPTDSGRKVSHHEYLELDPAQNLAVKETCEKLRISPFHFHVAVLRALIGGYTNIDDMCIGVVDANRGDERFAQTVGCFVNMLPVRVEAPSDATFADIARSASRKALMAFAHSSAPLDMILDAVKAPRSSETTPLFQVAVNYRTGGVWDLPMGDCQMKLSLTDGKDAENPFDISLGIAETGKGCVIEMHCQKTLYSSDATRTLLNTYLRLVDTFCKNTHVKLKDCVIHDQAKVSEALQIGKGPTTDFGWPSTLSHRVLETCLKSPKNAAIQFKGELLSYEQLASRIHLVAAAIVRAGASKGSRVAVLCEPSADAIISMLATLHIGGVYIPMDVSLPTARHAAMMNGGQPTLLLSHAATKHRVEDLVNETGSTISVLQVDTISSVEEKETVSCAAEPHNNAVLLFTSGSTGTPKGIMLSQANFVNHLALKTDRLQLGQENVLQQSSMGFDMSLIQMFCALANGGCLVIAPSEMRRDPVELTNLVHNSQISLTIATPSEYLAWLRYGTASLKDHTIWRHACMGGEPVSRQLKTEFWRLDLANLQLTNCYGPTEITAAATFETIRLDDQDDDNDRAQHAVGKALPNYSVRILDTAGRPQPVDHIGEICIGGASVALGYLGLPEQTKAKFTVDPVSGERLYLTGDKGKLLSDGTLLCLGRLDGDTQIKHRGLRIELQEVESALIQTANGLFSSAVVSARGSILVAHATISQSQAEPSESDLAKILSRLKLPQYFIPATIGILPTMPTTANGKLDRKAIASLPLPQKVTGEEGPQEKMNIREGELRLLWERVLPDTATTTPLGPSSDFFLCGGNSMLLMKLQAAIKESIGIEISTRVLYQASTLREMALCVDEQREEQADALEQHFDWQAETSLPKWLLDQIEDLPKTTKQPPKPNGIDILMTGATSFIGGRLLRSLVRSPSVRKVHCVAVLADEQDQLYQDEKVKCYTGSLLSSTLGLNNGERDQLARNVDVVIHAGSSGHCLNTYGSLRTPNLVSLQFLASLALPRSIPLLLLSSNRVPLLSGNTALPPTSVAAFPPATDGREGYTATKWASEVFLEKLVGAVQKKAPRPWVASVHRPCVVVSEHAPNSDALNAILRYSASMKCVPHLESATGYLDFASVESIVDSMAESAIEMATGNVTDQPSIRFQHHSGGVKVPIGDFKVHMENVYGGNFEEVHLEEWMHRAAAAGLDPLITAYMEGIIEAGAPIVFPYLGETV