Protein: Fumitremorgin C synthase (EC 1.14.19.71) (Cytochrome P450 monooxygenase ftmP450-2) (Fumitremorgin biosynthesis protein E) (Q4WAW8)
Organism: Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293) (Neosartorya fumigata)
Function: Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of fumitremorgins, indole alkaloids that carry not only intriguing chemical structures, but also interesting biological and pharmacological activities. The biosynthesis of fumitremorgin-type alkaloids begins by condensation of the two amino acids L-tryptophan and L-proline to brevianamide F, catalyzed by the non-ribosomal peptide synthetase ftmA. Brevianamide F is then prenylated by the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl diphosphate, resulting in the formation of tryprostatin B. The three cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively. The putative methyltransferase ftmMT/ftmD is expected for the conversion of 6-hydroxytryprostatin B to tryprostatin A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate, resulting in the formation of fumitremorgin B. Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via the insertion of an endoperoxide bond between the two prenyl moieties. In some fungal species, verruculogen is further converted to fumitremorgin A, but the enzymes involved in this step have not been identified yet (Probable).
Subcellular location: Membrane {ECO:0000255}; Single-pass membrane protein {ECO:0000255}.
Sequence: MERLPLSPAVLFLIIVLPILYLWIRYTAPARPHGKHLSLPPGPPRLPKIGNLHQVPRQIPWKKYKEWSDTYGPIMSVQLADTIAVVFSSWDLIKNHIERRNTIYSSRPSVPFFLHATGGLNASILPYGPEWKLQRAIRSSVLKPSMTVKYRDVQHVETTQLLHELLSTNDFPVCLRRCIASVFLTVAYGERCVDHAGLEAIDRLEELNRAIALHAEALFSGAAGILTQLVLPKALVDRLPVRWKKDADMLHNRLTADLVARTRAALVRPGWNWVKEFSMKDGIGSGDGDGEQGSKVELKRLAYMVGSLYEASMAASQALRVIILAGLLHPDATRRMHDELDAVVGTGRLPDFHDAAQLPYTQAFIKEAMRWRSLTPMGSPRATSDEDECRGYHIPCGATVLVNVWAINHDEAIFLDPFAFQPERWIENPDLPQLMYGMGQRACPGRHMGQDSLFLATARLFWAFDMALPDGADPIDQERFLDSGTTLAAFLPDFEVRFTPRSEKYQEVIENSMAVLPDVLSISATP
InterPro domains: - IPR001128: Cytochrome P450 (family) [40-479]
- IPR002401: Cytochrome P450, E-class, group I (family) [68-466]
- IPR036396: Cytochrome P450 superfamily (homologous_superfamily) [33-516]
- IPR050364: Cytochrome P450 monooxygenase, fungi (family) [11-513]
Interaction partners: - Fumitremorgin C monooxygenase
- 6-hydroxytryprostatin B O-methyltransferase
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0004497 (monooxygenase activity), GO:0016705 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen), GO:0016709 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen)
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:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:1901615 (organic hydroxy compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006066 (alcohol metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0018904 (ether metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:1901503 (ether biosynthetic process), GO:0009821 (alkaloid biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0019751 (polyol metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:0009820 (alkaloid metabolic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:0046165 (alcohol biosynthetic process), GO:0034311 (diol metabolic process), GO:0046173 (polyol biosynthetic process), GO:0035835 (indole alkaloid biosynthetic process), GO:0035834 (indole alkaloid metabolic process), GO:0034312 (diol biosynthetic 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)