Protein: Cytochrome P450 monooxygenase gsfF (EC 1.-.-.-) (Griseofulvin synthesis protein F) (D7PI20)
Organism: Penicillium aethiopicum
Function: Cytochrome P450 monooxygenase; 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.
Sequence: MTVLFILSAGLVAVFGYLVSWFIYCRTLHPLSKVPGPFWPSVTRLWLTYAVSRGELDVVQRDLHRRYGPLVRIAPDEIACADPEAIRKIYSTTSPLNKSDFYHIWDVGAFSKYPNAFAIVDENMHFERRRIVSSVYSMSTVLTLEPYIDNCSRLFVKRMTERTVPHEAIDLGDWFLWYAYDVIGELFFGHSLGFIENRGDEGGFLASLEVMLPVLTIAAASSPLVRGLIMGLFTLSSTARKGLKGMNHIIETARASVDKRASAVAEPGKGERKDLLHNLLNIVSSKGDKLDFGIEDVKNEAFAALTAGADATMIELQAIFYYLVKDRSVYEELRKEVDQAVETGKLSEFPSYSEVVQLPLLKATIKEALRLHPAVGFTMPRVVGQAGIELLGMYIPPGWKVGMNAAVVGRDEGVYGTDANTFRPERWIERTDSDMDRCNNLVFGAGTRTCIGKQIALSEIYKMVPLLIRKFDFALVDPSKSWTTHDYFFNKQSGVQVKVTVRGL
InterPro domains: - IPR036396: Cytochrome P450 superfamily (homologous_superfamily) [23-503]
- IPR017972: Cytochrome P450, conserved site (conserved_site) [443-452]
- IPR001128: Cytochrome P450 (family) [46-498]
- IPR002401: Cytochrome P450, E-class, group I (family) [316-473]
- IPR050121: Cytochrome P450 monooxygenase (family) [9-486]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase 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:0044281 (small molecule metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901615 (organic hydroxy compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006629 (lipid metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0120254 (olefinic compound metabolic process), GO:0006082 (organic acid metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0006066 (alcohol metabolic process), GO:0044249 (cellular biosynthetic process), GO:0009687 (abscisic acid metabolic process), GO:0120255 (olefinic compound biosynthetic process), GO:0006720 (isoprenoid metabolic process), GO:1902644 (tertiary alcohol metabolic process), GO:0043436 (oxoacid metabolic process), GO:0016053 (organic acid biosynthetic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:0008299 (isoprenoid biosynthetic process), GO:0046165 (alcohol biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0019752 (carboxylic acid metabolic process), GO:1902645 (tertiary alcohol biosynthetic process), GO:0046394 (carboxylic acid biosynthetic process), GO:0006721 (terpenoid metabolic process), GO:0016114 (terpenoid biosynthetic process), GO:0043288 (apocarotenoid metabolic process), GO:0072330 (monocarboxylic acid biosynthetic process), GO:0016106 (sesquiterpenoid biosynthetic process), GO:0032787 (monocarboxylic acid metabolic process), GO:0006714 (sesquiterpenoid metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0043229 (intracellular organelle), GO:0005783 (endoplasmic reticulum), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)