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 (PubMed:16262793, PubMed:16517624, PubMed:18427109). The ZEA backbone is synthesized from a single acetyl-CoA molecule and eight malonyl-CoA molecules (PubMed:16262793, PubMed:16517624, PubMed:18427109). 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 (PubMed:16262793, PubMed:16517624, PubMed:16751498, PubMed:18427109). 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 (PubMed:16262793, PubMed:16517624, PubMed:18427109). ZEA1 must be able to interact with ZEA2 to facilitate starter-unit acyltransfer and initiate polyketide biosynthesis (PubMed:18427109). ZEA1 also mediates the required C2-C7 cyclization to form the resorcylate core and catalyzes the formation of the macrolactone (PubMed:18427109). ZEB1 is then responsible for the chemical conversion of beta-zearalenonol (beta-ZOL) to ZEA in the biosynthetic pathway (PubMed:16262793).
Sequence
MSVDNKQVPGPVAIVGLACRFPGDATSPSKFWDLLKSGKDAYSETTDRYNAQAFYHPNSKRQNVLPVTGGHFLKQDPHVFDAAFFNITAAEAISLDPKQRIALEVAYEAFENAGKPLKQVAGTTTACFVGSSMSDYRDAVVRDFAHNPKYHVLGTCEEMIANRISHFFDIHGPSATVHTACSSSLVAIHLACQSLLSGDAEMALAGGVGMILTPDGTMQLNNLGFLNPEGHSRSFDKDAGGYGRGEGCGILVLKKLDKAIQDGDNIRAVIRASGVNSDGWTQGVTMPSSEAQAALIKHVYETRGLDYGATQYVEAHGTGTKAGDPVETGAIHRTIGQGASKNRKLWVGSVKPNIGHLEAAAGVASVIKGVLAMENSLIPPNIHFASPNPEIPLDEWNMAVPTKLTPWPAARTKRMSVSGFGMGGTNGHVVLEAFNSTPQSILYGDAQYQPAHNGKRLFTFSSHDQAGLDRVSKSLVDHLDSLGPAGARPEYLADLGYSLSVGKSGLSWKTAHLAESLTELREKLSSPQSEHAVREPRSQPKIGFVFTGQGAQWARMGVEMLHRPVFKESVQRSTDYLQQLGCDWTPIVELSRAQKESRLTLPEISQPICSVLQIALVDELRSWGVAPVSVVGHSSGEIAAAYCIEALSHKDAIAVAYFRGKVSAGLNHLNGGMMAVGCSRAEAETLIDESDLQGGHVTVACVNSPSNVTLSGDVAPLDQLKGILEKRGIFARRLRVEVAYHSTHMNSVFADYTASIADIEPQSCPSHQPIMVSSVTNNQVDPALLGSYYWGRNLISPVLFSDTIKEMVSPADGNGQKAVDLLVEIGPHGALGGPIEQILSHFDIENVGYQSMLTRGQNAVETSLELATSLFLQGVAIDIQKVNGDSGCRLLTNLPPYPWNHSKKFRAESRLQRELIAQSTPTRSIIGAPVPKMNESQRVWRGFIRLDDEPWIRGHTVGTTVLFPGAGMVSIVLEAAQQMVDPGKVARAFRLRDVSFSAAMALPEDQATEVIIQMKPQLVATSGSTPATWWEFTVSSCAGTDQLRDNCRGLITIDYEGNTSQQMAHEDSQVVSGRISDYHQILEECPATYAKDRFYKHMMKAAWRYGETFQGVENCHPGDGKTVFDVKLIDIGETFSKGQLDRPFLIHGATLDAVFQGWLGSTYKNGTFEFDKPFVPTKIGEMEISFNVPSEAGYMMPGLCRSHRSGFNELSADTIMFDKDLSRVILSVIDFRTSELEMDGAATEETTVEVDPADITSKVLWDYSLSLMEPCDLKQVMGSIVAQNSLTDFVRMLLHDNPAANIVEFISRSDGLPNTYASKLPPGTILPTQIRYAVVDETEDVGDENAASSMLTIDALVDSVSASGATADIVVIPQGFQFQDNYAKILEPLAKVSKPNTTIVVAVDTPDTTVPLKAKGFQLLHSIQGTPSLEVFAGLTGEQEKPTNGIHKEEVVLLLPSMLSTVTKEFAEEVQLDLEGQGFSVSTESLAESIDDSTFDGKTCVSLLEVERPLLDSLSESDFQLIRKVVLTSQRILWVTHGESPSLALVDGFSRCIMSEIEGVKFQVLHLSEPTGLQHGPRLAAKVIASKASDNEFRDKDGLLQVARIFKGLTENENIRHHLHDDVRVTRLSNQEHPLRLTIGKPGLLDTLYFVDDERVLAPLADHEVEIQVKATGLNFRDVMASMALVPVKGLGQEASGIVLRTGRDATHLKPGDRVSTLDMGTHATVMRADHRVTVKIPDAMSFEEAAAVPVVHTTAYYALVRLAKLQRGQSVLIHAAAGGVGQAALQLANHLGLVVYATVGSDDKRKLLTDTYQVSEDHIFNSRDASFAKGIMRVTGGRGVDCVLNSLSGELLRVSWSCLATFGTFVEIGLRDITNNMLLDMRPFSKSTTFSFINMYTLFEEDPSALGDILEEVFKLLGGGILQTPSPMTVYPINQVEDAFRIMQQGKHRGKIVLSFPDDAQAPVLHVAKNSMKLDSQATYLFVGGLGGLGRSLAKEFVSCGAKNIAFISRSGDSTSEAKATIKEITSRGANVKAYAADISNETAFLNAMKECSREFPPIKGVVQMAMVLRDVVFEKMTYEEWKLPLKPKVQGSWNLHKYFDHERPLDFMVICSSSSGIYGYPSQAQYAAGNTYQDALAHYRRAQGLRAVSVNLGIMRDVGVLAEQGTSGNIKLWEEVLGIREPAFHALMKSLIKGQTDNNSEFPAQICTGLGTADIMATHGLAKPTYFQDPRFGPLAVTSLSSDASGDKQSTAMSISSQLSEASSKAKATEIITNALIGKVADILQMPQSEVDPGQPLYRYGVDSLVALEVRNWITREMKVNVALLEILAAVPMESFAGKLASTSKLVTVS