Function
Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of the indole diterpenes penitrems (PubMed:26213965). The geranylgeranyl diphosphate (GGPP) synthase penG catalyzes the first step in penitrem biosynthesis via conversion of farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP) (Probable). Condensation of indole-3-glycerol phosphate with GGPP by the prenyl transferase penC then forms 3-geranylgeranylindole (3-GGI) (Probable). Epoxidation by the FAD-dependent monooxygenase penM leads to a epoxidized-GGI that is substrate of the terpene cyclase penB for cyclization to yield paspaline (Probable). Paspaline is subsequently converted to 13-desoxypaxilline by the cytochrome P450 monooxygenase penP, the latter being then converted to paxilline by the cytochrome P450 monooxygenase penQ (PubMed:26213965). Paxilline is converted to beta-paxitriol via C-10 ketoreduction by the short-chain dehydrogenase PC-15 which can be monoprenylated at the C-20 by the indole diterpene prenyltransferase penD (Probable). A two-step elimination (acetylation and elimination) process performed by the O-acetyltransferase PC-16 and the P.simplicissimum ptmI-ortholog not yet identified in P.crustosum, leads to the production of the prenylated form of penijanthine (Probable). The FAD-linked oxidoreductase ptmO then converts the prenylated form of penijanthine into PC-M5 which is in turn transformed into PC-M4 by the aromatic dimethylallyltransferase PC-22 (Probable). A series of oxidation steps involving 4 cytochrome P450 monooxygenases (PC-21, PC-05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14) are required for the transformation of PC-M4 to penitrems A and E. Synthesis of these final products is proposed to proceed via penitrems D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-14, PC-23) (Probable).
Sequence
MTVMVSRIEYIGQIVRGEATVIWILVALVLVAYLILPNPTYRTNVKVPTVRYLGGWMPDLVDRLFFNTKATSVIYDGYKQYKKKAYKVLKADGDLVVLSTRYAEELRQLPASTLNALEATFTDHVGDYTTILTDSHLHTETIQKRLTPAIGRLIPRIISELDHAYEVEFPKCDGKWVAINPYEVFLRLVARVGARIFIGDTLCRDEQWLKASIDYTKNIFVTIALLRPVPGFLQPLVGRVLPSSRSLNHQLAYIKNEFLGPLIEKRREMESSGDPNYEKPDDFLQWMMDLAKTEQESHPHNLAQRLLGITSMAVVHTSAMSLTHILYDLLVMPQWLQPLRDEIQEVNPDWHSTTQAHLIGLKGMDSFLKESQRFNPPGELSFHRVVKHDLTLSDGLFLPKGTHICMAAGPISRDADVMSDPDTFDAFRFVKENRPTSGFVSTGATNMHFGLGRYACPGRFFAAFVMKAILSRFLADYDFRFGPDQKDRPKNMMIGDKIVPNVSTPIFIRKRTTSKPL