Protein: Non-reducing polyketide synthase gsfA (EC 2.3.1.-) (Griseofulvin synthesis protein A) (Norlichexanthone synthase) (D7PI15)
Organism: Penicillium aethiopicum
Function: Norlichexanthone synthase; part of the gene cluster that mediates the biosynthesis of griseofulvin, an important antifungal drug that has been in use for a long time for treating dermatophyte infections. The first step of the pathway is the formation of the heptaketide backbone by gsfA which is initiated by priming with acetyl-CoA, followed by sequential condensations of 6 malonyl-CoA units. The resulting benzophenone can undergo a spontaneous dehydration to form norlichexanthone. However, the true precursor for the griseofulvin biosynthesis is not norlichexanthone, but the heptaketide benzophenone that is O-methylated at 3-OH by gsfB to produce griseophenone D which is further methylated at 9-OH by gsfC to yield griseophenone C. Griseophenone C is then substrate of halogenase gsfI which is responsible for the regio-specific chlorination at the C13 position to form griseophenone B. The cytochrome P450 gsfF catalyzes the coupling of orcinol and phloroglucinol rings in griseophenone B to form desmethyl-dehydrogriseofulvin A which is further methylated at 5-OH by gsfD to yield dehydrogriseofulvin. Finally, gsfE performs stereospecific reduction of enone 18 of dehydrogriseofulvin to afford the final product griseofulvin.
Interaction partners:
Sequence:
MTSAKVLYFSGEIPQGDPEGDQRTLFRKLHLLSKERDHVVLASLLECVTLTLKDECSKLSPQYRDLLPPFESVLDLTDHVVQLRKTPLGGAIERVLVLVFQLGSLVAYHEAHPLEYNFTPASTVIIGRGSGLLSAAAIGLSPSIVMVPSIAKEIARISFRFGLVVDKVCRSLEVSSDEINSDGAWVYCVHGIGEKEARDAVNQFNEIKAYPSTNGASVFNVDDAGNSVSIGGPPKTLEALFSESNIFKKTKNVAMRKIQGMWHTDRVYGPEHVEQIVPKIESARELHVPLISPVSGDPFRETEAGPLLEQIMEEILMERVRWDMIIETVSKQLKQLMPKSVQLVSIQPSHYNQNMLERWKSELPDAAVSGLTMMPAILELALEQSPPKDTRSSKIAVVGMSCRFPGSDTTEEFWERLMLGEDMHRHIPPDRFDVETHVDPTGKRHNTSKTSYGCFVDNPGLFDAMFFGMSPREAEQTDPMQRLALVTAYEALEKAGYVDGRGVIHRKRVGTFYGQASDDYREVNSGQEVGTYFIPGGCRAFGPGRINYFLNFWGPSFSVDTACSSSLAAIQAACSSLWSGDIDMAITGGMNILSNSDVYAGLSQGHFLSPTGGCKTWDEGADGYCRSDGVGSVVLKRLEDAEADNDNILAVVLSAATSHSAEAVSITHPHDAAQALLYNQIVRRAGIDPLEVGYVEMHGTGTQAGDPTEMRSVTSVFAPPHIQGSRPIPLHVGSVKANMGHGEAAAGIMAFVKTMLVFQNGIIPPHIGVKTGLNPALPDLDKAGVVIPFRAANWRPTGTKKRLAMVNNFGAAGGNTAMIIEEAKARPRLCEDIREAHAITISAKTAVSLSLNIKRLVEYIESAQDLSLADVAYTVSARRRHYEYRKSVVVRSLAEAIKHLQPHIETAKSQTPTLVKRPPVAFAFAGQGTFYVGIAAQIYRDSPFFRAQIDQFDNLARRQNFPSFLPAINKTCAHEDLPASSIHLAIVCVEVALARMCMTFGIKPCAVIGHSLGEYAALAVAEVLSDSDTVFLVGTRATILESNCSPYTHGMISVRASVDDISREADGLPFEVSCINGPNETVIGGTVENLEAVADRLSKVGYRKTRLDVPHAYHTAQMDNVVNELIRQSQGIAYNTPKIPIMSPRDSSVIETGANIDSSYLPTSLKKAVDFAGALNAAWEAGVVSKSTVWLELSHHPVCSGFINRTLPNTSLTCSTLHRDSDNWTSLLKTLSSLYEVGLNIDWNEYHRPFEHALRLVSAPTYAWNNKDYWIQYRGDWNLTKGQVLPEAELPAVSGFRTSSIHRLYSENYDSSTAHLLGECNMTDLSLKGVIEGHAMNGYGVASSFLHAEMAFTLARRIQEKASLSTFTGMGINVTNFEYHDPVVKDASSLDPYPIVVDAEANLEMGEVQIKWFNPAIEKWYCHAIAYYEDPSTWLSNWSRTTRLVTSRIDALVAMSNKGMANKLTTSLAYTLFGKLVDYSSMYHTMQWVILNEDEAVAEVVFPADTQGDWAVPPHFIDGVVSLSGFILNGGTHFDNVNNFFITPSWKSMRFAKPLAPGGRYLTYVRMIPEGVDDKGRLGSYVGDVYILQDGEIVGVVEAILFRQWPRIMLNRFFQPVGMAPPAPRVEKKRDAGRGTLPSSSSLQEKTTATAVTAKITARFPGSVITPSRSAPISKSGSSPKIVPQLDYSLLTPRTSPNSDERIEKTDSDSGFEEADGANDVTSRAVEILAEELAVDKGLLTDECEIADIGVDSLMSLVISQKLREDLGIEVRDAFYLEVTTIGDLKKLLS