Protein: Highly reducing polyketide synthase ZEA2 (A0A098D8A0)
Organism: Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
Function: Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of zearalenone (ZEA), a nonsteroid estrogen that is a contaminant of cereal grains and causes estrogenic disorders in humans and animals. The ZEA backbone is synthesized from a single acetyl- CoA molecule and eight malonyl-CoA molecules. The reducing polyketide synthase ZEA2 is proposed to synthesize a reduced hexaketide intermediate by using different combinations of its reductive domains during each round of condensation. The hexaketide thioester is then transacylated to the non-reducing polyketide synthase ZEA1 and is further condensed with three malonyl-CoAs without reductive tailoring to yield a mixed reduced/unreduced nonaketide. ZEA1 must be able to interact with ZEA2 to facilitate starter-unit acyltransfer and initiate polyketide biosynthesis. ZEA1 also mediates the required C2-C7 cyclization to form the resorcylate core and catalyzes the formation of the macrolactone. ZEB1 is then responsible for the chemical conversion of beta-zearalenonol (beta-ZOL) to ZEA in the biosynthetic pathway
Sequence: MSVDNKQVPGPVAIVGLACRFPGDATSPSKFWDLLKSGKDAYSETTDRYNAQAFYHPNSKRQNVLPVTGGHFLKQDPHVFDAAFFNITAAEAISLDPKQRIALEVAYEAFENAGKPLKQVAGTTTACFVGSSMSDYRDAVVRDFAHNPKYHVLGTCEEMIANRISHFFDIHGPSATVHTACSSSLVAIHLACQSLLSGDAEMALAGGVGMILTPDGTMQLNNLGFLNPEGHSRSFDKDAGGYGRGEGCGILVLKKLDKAIQDGDNIRAVIRASGVNSDGWTQGVTMPSSEAQAALIKHVYETRGLDYGATQYVEAHGTGTKAGDPVETGAIHRTIGQGASKNRKLWVGSVKPNIGHLEAAAGVASVIKGVLAMENSLIPPNIHFASPNPEIPLDEWNMAVPTKLTPWPAARTKRMSVSGFGMGGTNGHVVLEAFNSTPQSILYGDAQYQPAHNGKRLFTFSSHDQAGLDRVSKSLVDHLDSLGPAGARPEYLADLGYSLSVGKSGLSWKTAHLAESLTELREKLSSPQSEHAVREPRSQPKIGFVFTGQGAQWARMGVEMLHRPVFKESVQRSTDYLQQLGCDWTPIVELSRAQKESRLTLPEISQPICSVLQIALVDELRSWGVAPVSVVGHSSGEIAAAYCIEALSHKDAIAVAYFRGKVSAGLNHLNGGMMAVGCSRAEAETLIDESDLQGGHVTVACVNSPSNVTLSGDVAPLDQLKGILEKRGIFARRLRVEVAYHSTHMNSVFADYTASIADIEPQSCPSHQPIMVSSVTNNQVDPALLGSYYWGRNLISPVLFSDTIKEMVSPADGNGQKAVDLLVEIGPHGALGGPIEQILSHFDIENVGYQSMLTRGQNAVETSLELATSLFLQGVAIDIQKVNGDSGCRLLTNLPPYPWNHSKKFRAESRLQRELIAQSTPTRSIIGAPVPKMNESQRVWRGFIRLDDEPWIRGHTVGTTVLFPGAGMVSIVLEAAQQMVDPGKVARAFRLRDVSFSAAMALPEDQATEVIIQMKPQLVATSGSTPATWWEFTVSSCAGTDQLRDNCRGLITIDYEGNTSQQMAHEDSQVVSGRISDYHQILEECPATYAKDRFYKHMMKAAWRYGETFQGVENCHPGDGKTVFDVKLIDIGETFSKGQLDRPFLIHGATLDAVFQGWLGSTYKNGTFEFDKPFVPTKIGEMEISFNVPSEAGYMMPGLCRSHRSGFNELSADTIMFDKDLSRVILSVIDFRTSELEMDGAATEETTVEVDPADITSKVLWDYSLSLMEPCDLKQVMGSIVAQNSLTDFVRMLLHDNPAANIVEFISRSDGLPNTYASKLPPGTILPTQIRYAVVDETEDVGDENAASSMLTIDALVDSVSASGATADIVVIPQGFQFQDNYAKILEPLAKVSKPNTTIVVAVDTPDTTVPLKAKGFQLLHSIQGTPSLEVFAGLTGEQEKPTNGIHKEEVVLLLPSMLSTVTKEFAEEVQLDLEGQGFSVSTESLAESIDDSTFDGKTCVSLLEVERPLLDSLSESDFQLIRKVVLTSQRILWVTHGESPSLALVDGFSRCIMSEIEGVKFQVLHLSEPTGLQHGPRLAAKVIASKASDNEFRDKDGLLQVARIFKGLTENENIRHHLHDDVRVTRLSNQEHPLRLTIGKPGLLDTLYFVDDERVLAPLADHEVEIQVKATGLNFRDVMASMALVPVKGLGQEASGIVLRTGRDATHLKPGDRVSTLDMGTHATVMRADHRVTVKIPDAMSFEEAAAVPVVHTTAYYALVRLAKLQRGQSVLIHAAAGGVGQAALQLANHLGLVVYATVGSDDKRKLLTDTYQVSEDHIFNSRDASFAKGIMRVTGGRGVDCVLNSLSGELLRVSWSCLATFGTFVEIGLRDITNNMLLDMRPFSKSTTFSFINMYTLFEEDPSALGDILEEVFKLLGGGILQTPSPMTVYPINQVEDAFRIMQQGKHRGKIVLSFPDDAQAPVLHVAKNSMKLDSQATYLFVGGLGGLGRSLAKEFVSCGAKNIAFISRSGDSTSEAKATIKEITSRGANVKAYAADISNETAFLNAMKECSREFPPIKGVVQMAMVLRDVVFEKMTYEEWKLPLKPKVQGSWNLHKYFDHERPLDFMVICSSSSGIYGYPSQAQYAAGNTYQDALAHYRRAQGLRAVSVNLGIMRDVGVLAEQGTSGNIKLWEEVLGIREPAFHALMKSLIKGQTDNNSEFPAQICTGLGTADIMATHGLAKPTYFQDPRFGPLAVTSLSSDASGDKQSTAMSISSQLSEASSKAKATEIITNALIGKVADILQMPQSEVDPGQPLYRYGVDSLVALEVRNWITREMKVNVALLEILAAVPMESFAGKLASTSKLVTVS
InterPro domains: - IPR020843: Enoylreductase domain (domain) [1643-1955]
- IPR006162: Phosphopantetheine attachment site (ptm) [2301-2316]
- IPR014043: Acyl transferase domain (domain) [544-876]
- IPR036736: ACP-like superfamily (homologous_superfamily) [2272-2345]
- IPR016035: Acyl transferase/acyl hydrolase/lysophospholipase (homologous_superfamily) [541-851]
- IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [1741-2166]
- IPR001227: Acyl transferase domain superfamily (homologous_superfamily) [541-847]
- IPR020841: Polyketide synthase, beta-ketoacyl synthase domain (domain) [9-436]
- IPR016039: Thiolase-like (homologous_superfamily) [6-491]
- IPR011032: GroES-like superfamily (homologous_superfamily) [1655-1774]
- IPR020807: Polyketide/metazoan fatty acid synthase-like, dehydratase domain (domain) [923-1112]
- IPR013154: Alcohol dehydrogenase-like, N-terminal (domain) [1662-1738]
- IPR018201: Beta-ketoacyl synthase, active site (active_site) [172-188]
- IPR032821: Polyketide synthase, C-terminal extension (domain) [387-480]
- IPR014031: Beta-ketoacyl synthase, C-terminal (domain) [268-384]
- IPR016036: Malonyl-CoA ACP transacylase, ACP-binding (homologous_superfamily) [670-736]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [2267-2346]
- IPR020806: Polyketide synthase-like, phosphopantetheine-binding domain (domain) [2275-2346]
- IPR014030: Beta-ketoacyl synthase-like, N-terminal (domain) [11-259]
- IPR013968: Polyketide synthase-like, ketoreductase domain (domain) [1979-2159]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0016491 (oxidoreductase activity), GO:0016746 (acyltransferase activity), GO:0016741 (transferase activity, transferring one-carbon groups), GO:0016747 (acyltransferase activity, transferring groups other than amino-acyl groups), GO:0008168 (methyltransferase activity), GO:0008757 (S-adenosylmethionine-dependent methyltransferase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0016999 (antibiotic metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0017000 (antibiotic biosynthetic process), GO:1901615 (organic hydroxy compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0033067 (macrolide metabolic process), GO:0030638 (polyketide metabolic process), GO:1901334 (lactone metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0033068 (macrolide biosynthetic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:0030639 (polyketide biosynthetic process), GO:0018958 (phenol-containing compound metabolic process), GO:0043386 (mycotoxin biosynthetic process), GO:1901336 (lactone biosynthetic process), GO:0046189 (phenol-containing compound biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)