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 (PubMed:20534346, PubMed:23978092). 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 (PubMed:20534346). O-methylation at 3-OH by gsfB leads to griseophenone D which is further methylated at 9-OH by gsfC to yield griseophenone C (PubMed:23978092). Griseophenone C is then substrate of halogenase gsfI which is responsible for the regio-specific chlorination at the C13 position to form griseophenone B (PubMed:23978092). 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 (PubMed:23978092). Finally, gsfE performs stereospecific reduction of enone 18 of dehydrogriseofulvin to afford the final product griseofulvin (PubMed:23978092).
Sequence
MTSAKVLYFSGEIPQGDPEGDQRTLFRKLHLLSKERDHVVLASLLECVTLTLKDECSKLSPQYRDLLPPFESVLDLTDHVVQLRKTPLGGAIERVLVLVFQLGSLVAYHEAHPLEYNFTPASTVIIGRGSGLLSAAAIGLSPSIVMVPSIAKEIARISFRFGLVVDKVCRSLEVSSDEINSDGAWVYCVHGIGEKEARDAVNQFNEIKAYPSTNGASVFNVDDAGNSVSIGGPPKTLEALFSESNIFKKTKNVAMRKIQGMWHTDRVYGPEHVEQIVPKIESARELHVPLISPVSGDPFRETEAGPLLEQIMEEILMERVRWDMIIETVSKQLKQLMPKSVQLVSIQPSHYNQNMLERWKSELPDAAVSGLTMMPAILELALEQSPPKDTRSSKIAVVGMSCRFPGSDTTEEFWERLMLGEDMHRHIPPDRFDVETHVDPTGKRHNTSKTSYGCFVDNPGLFDAMFFGMSPREAEQTDPMQRLALVTAYEALEKAGYVDGRGVIHRKRVGTFYGQASDDYREVNSGQEVGTYFIPGGCRAFGPGRINYFLNFWGPSFSVDTACSSSLAAIQAACSSLWSGDIDMAITGGMNILSNSDVYAGLSQGHFLSPTGGCKTWDEGADGYCRSDGVGSVVLKRLEDAEADNDNILAVVLSAATSHSAEAVSITHPHDAAQALLYNQIVRRAGIDPLEVGYVEMHGTGTQAGDPTEMRSVTSVFAPPHIQGSRPIPLHVGSVKANMGHGEAAAGIMAFVKTMLVFQNGIIPPHIGVKTGLNPALPDLDKAGVVIPFRAANWRPTGTKKRLAMVNNFGAAGGNTAMIIEEAKARPRLCEDIREAHAITISAKTAVSLSLNIKRLVEYIESAQDLSLADVAYTVSARRRHYEYRKSVVVRSLAEAIKHLQPHIETAKSQTPTLVKRPPVAFAFAGQGTFYVGIAAQIYRDSPFFRAQIDQFDNLARRQNFPSFLPAINKTCAHEDLPASSIHLAIVCVEVALARMCMTFGIKPCAVIGHSLGEYAALAVAEVLSDSDTVFLVGTRATILESNCSPYTHGMISVRASVDDISREADGLPFEVSCINGPNETVIGGTVENLEAVADRLSKVGYRKTRLDVPHAYHTAQMDNVVNELIRQSQGIAYNTPKIPIMSPRDSSVIETGANIDSSYLPTSLKKAVDFAGALNAAWEAGVVSKSTVWLELSHHPVCSGFINRTLPNTSLTCSTLHRDSDNWTSLLKTLSSLYEVGLNIDWNEYHRPFEHALRLVSAPTYAWNNKDYWIQYRGDWNLTKGQVLPEAELPAVSGFRTSSIHRLYSENYDSSTAHLLGECNMTDLSLKGVIEGHAMNGYGVASSFLHAEMAFTLARRIQEKASLSTFTGMGINVTNFEYHDPVVKDASSLDPYPIVVDAEANLEMGEVQIKWFNPAIEKWYCHAIAYYEDPSTWLSNWSRTTRLVTSRIDALVAMSNKGMANKLTTSLAYTLFGKLVDYSSMYHTMQWVILNEDEAVAEVVFPADTQGDWAVPPHFIDGVVSLSGFILNGGTHFDNVNNFFITPSWKSMRFAKPLAPGGRYLTYVRMIPEGVDDKGRLGSYVGDVYILQDGEIVGVVEAILFRQWPRIMLNRFFQPVGMAPPAPRVEKKRDAGRGTLPSSSSLQEKTTATAVTAKITARFPGSVITPSRSAPISKSGSSPKIVPQLDYSLLTPRTSPNSDERIEKTDSDSGFEEADGANDVTSRAVEILAEELAVDKGLLTDECEIADIGVDSLMSLVISQKLREDLGIEVRDAFYLEVTTIGDLKKLLS