ID   FLVC_ASPFN              Reviewed;         538 AA.
AC   B8NHD8;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=Cytochrome P450 monooxygenase flvC {ECO:0000303|PubMed:31885262};
DE            EC=1.-.-.- {ECO:0000269|PubMed:31885262};
DE   AltName: Full=Flavunoidine biosynthesis cluster protein C {ECO:0000303|PubMed:31885262};
GN   Name=flvC {ECO:0000303|PubMed:31885262}; ORFNames=AFLA_135430;
OS   Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS   / JCM 12722 / SRRC 167).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=332952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC   167;
RX   PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA   Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA   Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT   "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT   aflatoxin contamination of food and feed.";
RL   Genome Announc. 3:E0016815-E0016815(2015).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=31885262; DOI=10.1021/jacs.9b13046;
RA   Yee D.A., Kakule T.B., Cheng W., Chen M., Chong C.T.Y., Hai Y., Hang L.F.,
RA   Hung Y.S., Liu N., Ohashi M., Okorafor I.C., Song Y., Tang M., Zhang Z.,
RA   Tang Y.;
RT   "Genome mining of alkaloidal terpenoids from a hybrid terpene and
RT   nonribosomal peptide biosynthetic pathway.";
RL   J. Am. Chem. Soc. 142:710-714(2020).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of flavunoidine, an alkaloidal terpenoid with
CC       a tetracyclic cage-like core connected to dimethylcadaverine via a C-N
CC       bond and acylated with 5,5-dimethyl-L-pipecolate (PubMed:31885262). The
CC       tetracyclic core is synthesized by the terpene cyclase flvE and the
CC       cytochrome P450 monooxygenase flvD (PubMed:31885262). The terpene
CC       cyclase flvE catalyzes the cyclization of farnesyl pyrophosphate (FPP)
CC       to form (1R,4R,5S)-(+)-acoradiene and the cytochrome P450 monooxygenase
CC       flvD is then responsible for oxidative conversion of (1R,4R,5S)-(+)-
CC       acoradiene into the tetracyclic cage present in the final product
CC       flavunoidine (PubMed:31885262). The cytochrome monooxygenase flvC then
CC       hydroxylates the C-10 position (PubMed:31885262). The second terpene
CC       cyclase flvF is required for attachment of the C-7 axial
CC       dimethylcadaverine which is itself produced by the N-methyltransferase
CC       flvH and the decarboxylase flvG via methylation of L-lysine to give
CC       N,N-dimethyl-L-Lysine, and decarboxylation to afford
CC       dimethylcadaverine, respectively (PubMed:31885262). The NRPS flvI
CC       acylates the terpenoid core at the hydroxylated C-10 with
CC       dimethylpipecolate to yield final flavunoidine (PubMed:31885262). The
CC       bifunctional enzyme flvA and the dehydrogenase flvB are responsible for
CC       the synthesis of the dimethylpipecolate precursor (PubMed:31885262).
CC       The PLP-dependent lyase domain of flvA might use L-O-acetyl-homoserine
CC       and alpha-keto-isovalerate to form an intermediary ketone that can
CC       cyclize intramolecularly to yield an imine (PubMed:31885262). The imine
CC       can be reduced by flvB to yield the 6-carboxylated pipecolate
CC       (PubMed:31885262). The C-terminal alpha-KG-dependent oxygenase domain
CC       of flvA is then proposed to catalyze the decarboxylation to yield
CC       dimethylpipecolate (PubMed:31885262). {ECO:0000269|PubMed:31885262}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:31885262}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; EQ963478; EED50780.1; -; Genomic_DNA.
DR   RefSeq; XP_002379556.1; XM_002379515.1.
DR   EnsemblFungi; EED50780; EED50780; AFLA_135430.
DR   VEuPathDB; FungiDB:AFLA_135430; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   HOGENOM; CLU_001570_14_4_1; -.
DR   OMA; MEWRECI; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000001875; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..538
FT                   /note="Cytochrome P450 monooxygenase flvC"
FT                   /id="PRO_0000454479"
FT   TRANSMEM        17..37
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         478
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   538 AA;  60010 MW;  D0C14199C3429B79 CRC64;
     MDFGGILLHL EARSMATVLI AGLLVYWVGS AIFLAVLHPL AKFPGPKLAA ASDWWLVYHE
     WFLGKSLTDI LFDLHQNYGT INVPYGGLQD LWLDMDRIAY VVQSLTWESA LEANSLVKLH
     FSSMQAYSDI YNVKSKWDKD PEVYKAIVDT SSAFGLRNYH EAKERRDLIW PFYSRQSVQR
     MQKAINRQIS FLVDQLDKQN QEGKLSNMSM AFRCLAQDIM ADICLGKSFG TLEERDFGSP
     LIHALDEGLE SYVLMKSFPT LRNILYSISA MVTLPGEAEF ATYGTIVADH VTRGIQQPDT
     IPPNTMLGFL VPTSSNTAKE APQPKLSQGH MTEELQTFVI GAGETVASAM VQGLSGILQS
     PDLYKNVYEE IVQVWPETDG PVPPIEVLEK LPLLTAVIKE ALRLTHGVVT PLARVISAGG
     ACIDGHHVPG GTSVGTSHVF IHMSSDYYDA PDEFRPERWL GSSSDKHLVA FSKGPRGCMG
     INLAWCQLYL VLATLVRTVQ MEYPADLNDI KIKWKDCFQP LYYGRPLQVR CTRAEGHS