Protein: FUM1_GIBM7
Sequence: MGVIESPSSTTSGSAEEMAQAITGHEDSVLPVAIVGMGMRLPGGIHTPDELWGMLVEKRSTRCEIPPTRFSVDGFHSPSSKPGSIAMRHGHFLDDKDDLHRLDTSFFSMGMTEVSDIDPQQRMLLEVAYECMQSSGQTNWRGSNIGCYVGVWGEDWLDLHSKDLYDSGTYRVSGGHDFAISNRISYEYDLKGPSFTIKAGCSSSLIALHEAVRAIRAGDCDGAIVAGTNLVFSPTMSVAMTEQGVLSPDASCKTFDANANGYARGEAINAIFLKPLNNALREGDPIRALVRATSSNSDGKTPGMSMPSSESHEALIRRAYGEVFLDPKDTCFVEAHGTGTSVGDPLEATAIARVFGGSSDNKLYIGSVKPNLGHSEGASGVSSVMKAVLALENRTIPPNINFSTPNPKIPFSEMNMAVPVDAIPWPRDRPLRVSVNSFGIGGANAHCIIETLEEYLGRSLPNESQVAPIRNGNGSVQADSSSAVTSITAMKMEVRRKKRQSAVEAAGLVSNLRLVADSTKIRPSKALYVLSAANPTSLRQSVMDYQKYLASHKTDPVDVSYTLANRREHLSHRTYGVVTTESTNDTPIVPDFSPLSKTNNNSLPEINMIFTGQGAQWVGMGKELMDEYETFYNTIAYLGLVLSGLEHPPTWDLIRELSRPAESSNVGRAEFSQPLVCAVQVALVDLLRSWGITPAAVVGHSSGEMAAAYAAGAISSEEAITIAYYRGYVNQQYTRDGGMAAIGMGAQEVAPYLVEGVGVACENSPQSVTLSGDKGVLEEVCQKIKEQVPDCFVRQLKVNVAYHSHHMQDLGGLFENLLEGKVYSQSPTIPFFSSVTVQKITEPRSLDAAYWRQNLESPVRFTGAVKLLLEARASTGSKQVFVEIGPHSALSGPLRQIFKAHGRGKEAYVSAMIRGEDCTESLLKLAGELFCHGTSLQLSNVTADGDVVVDLPPYPWNHDREYWSESRVSKDWRFRKFPNHELLGSRTLESSSLQPEWRNLIRLDGIPWLRDHQVLNDVVFPCAGYLAMAVEAVRQVAGTSEIGGFTLKSVVVQSALVLTESKPVEVLTSLRPVRLTNTLDSAWWEFSIVAHNGTSWIKHCEGQVRPGQDAHQKTAVLPQSEPISQHYPRLVDNLYPELLRIGLRYGPSFRGLDNVSCVPNGKKAAAMLRETTVSESSYAIHPTTIDHCLQLFFPASCDGAFYRAEKLCVPTAIGRLYLADGKSCEVESARAEASAATNSGGSISGAATVVSKQNSTLLSLEDGKFSPLEMDLAEDGNADLVGTARLEWKPNLDFADMCSLVRPSHASMNDGPELDLVEQLTLLAILEIHERIDGAVTPGGHDHAHQHIPNFRGWIADQVTAAAEGRYRGVVADAREIASLERGARLSLMTNLRQQVLRTGAASAAVLIGRVVDHCEEIVKGELEGIELLQAEDGLTNYYNYVESRTDSIDFFATAGHTRPTLRVLEIGAGTGGGAQVILEGLTNGKERLFSTYAYTDISAGFFVAAQERFKAYKGLDFKVLDITKDPSEQGFESGSFDLIIAGNVIHATPTLNETLANVRKLLAPEGYLFLQELSPKMRMVNLIMGILPGWWLGAAEGRVEEPYLDPSQWDTVLKETGFSGVDSAIYDAPYPYHLNANIISRPAKESAPQPRAIRGRLTLLHHADDTNSSSITQLREVLDARGLETDMVVFHEHEELKAGEQDVIISLLELKKPFFSSISAAQLESFQRIVAKLGSIEMIWVTRPAQHGLSASDNPGFGLSLGLTRTLRSEQSLAITTLEIDQVNDESFKAVTNLAIKVLDHREGGSTESTRGATTMDPDREYVVENGVVKVARYHPVSLSQELASRASKPEAVTLEIGRMGLLQTLGWVPFPTSDPGYGEVTIEPRCAGLNFRDVLLCMGVVEATGVGIGLEGSGIITKVGAGVGKFQPGDPVFYLADNCFSTQITISAQRCAKIPSQLAFEDAATMPCVYATVIHSLLDVGGLRPGQSILIHSACGGIGIAALNLCRNFQGLEIYTTVGNEEKVQYLVDNFGLPRSRIFNSRDASFLYDVRAATQGRGVDLVLNSLSGDLLHASWQCVAPYGKMLEIGKRDFIGKARLEMDLFEANRSFIGIDLARFDSARCQKLLERTAAMIQTGIVQPIKPVKVFDASDAEGAFRYMQKGVHLGKIVVSIPPHSSTALPITPKPLQVKLNPEASYLLVGGLGGLGRAAATWMVESGARYLIFFSRSAGLSVRDQAFFQELASQGCTAQAVRGDVLNLADVELAMASAPPGKPIRGVLQMSMVLRDKPFADMSLEDWDTAVKPKVHGTWNLHLAAPKDLDFFFATGSISGSFGTPGQANYAAGNTYLTALFEHRRALGLPASVLQIGLIEDIGYLAKNPERAEALRAAGGFFLRTRQLLQGLNWALLSSDPHHPEYQLTIGLRSDKALSDPANRVIWKKDSRAALYHNQEISTDAGAGDDQGINAIRLLVASCEEDPGILEDPATVELVTNEIGKRVCMFMLRPVEEMDPTASLTSLGVDSLVTIEIRNWIKRTFGGVEVSTLEILNSGTIQGLARLTVDGLKARFAASEQTDGDAYLEMKAP
What is the function of this protein?
Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3 (FB3), and B4 (FB4), which are carcinogenic mycotoxins (PubMed:10413619, PubMed:12620260).  On the basis of the chemical structures of fumonisins and precursor feeding studies, fumonisin biosynthesis is predicted to include at least five groups of biochemical reactions: synthesis of a linear polyketide with a single terminal carbonyl function and methyl groups at C-10 and C-14; condensation of the polyketide with alanine; reduction of the polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide carbons; and esterification of six-carbon tricarboxylic acids to two of the hydroxyls (PubMed:12620260).  The biosynthesis starts with the polyketide synthase FUM1-catalyzed carbon chain assembly from one molecule of acetyl CoA, eight molecules of malonyl CoA, and two molecules of methionine (PubMed:10413619).  The C-18 polyketide chain is released from the enzyme by a nucleophilic attack of a carbanion, which is derived from R-carbon of alanine by decarboxylation, on the carbonyl carbon of polyketide acyl chain (PubMed:15137825, PubMed:12720383).  This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl transferase FUM8 (PubMed:15137825, PubMed:12720383).  The resultant 3-keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-12,16-dimethylicosane by reductase FUM13 (PubMed:12720383, PubMed:15137825).  Subsequent oxidations at C-5, C-10, C-14 and C-15 followed by tricarballylic esterification of the hydroxyl groups on C-14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782, PubMed:15137825, PubMed:16489749).  The C-10 hydroxylation is performed by the cytochrome P450 monooxygenase FUM2 and occurs early in the biosynthesis (PubMed:16536629).  The C-5 hydroxylation is performed by the dioxygenase FUM3 and occurs late in the biosynthesis (PubMed:20237561, PubMed:15066782, PubMed:15137825, PubMed:16536629).  Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for the two remaining hydroxylations at positions C-14 and C-15 (PubMed:12620260).  The FUM11 tricarboxylate transporter makes a tricarboxylic acid precursor available for fumonisin biosynthesis via its export from the mitochondria (PubMed:12620260).  If the precursor is citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of citrate to form tricarballylic acid either before or after the CoA activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed esterification of CoA-activated tricarballylic acid to the C-14 and C-15 hydroxyls of the fumonisin backbone (PubMed:16489749, PubMed:17147424).  Alternatively, if the precursor is cis-aconitate, FUM7 may function to reduce the double bond (PubMed:17147424).  In this alternate proposal, feeding studies with tetradehydro-fumonisin B1 suggests that FUM7 cannot function on the tricarballylic ester and must therefore act before the FUM14-mediated esterification (PubMed:17147424).
What are the official names of this protein?
Highly reducing polyketide synthase FUM1, HR-PKS FUM1, Fumonisin biosynthesis cluster protein 1.