ID   OLCE_PENCN              Reviewed;         465 AA.
AC   P9WEQ4;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 1.
DT   03-AUG-2022, entry version 4.
DE   RecName: Full=FAD-dependent monooxygenase olcE {ECO:0000303|PubMed:30090271};
DE            EC=1.-.-.- {ECO:0000269|PubMed:30090271};
DE   AltName: Full=15-deoxyoxalicine B biosynthesis cluster protein E {ECO:0000303|PubMed:30090271};
GN   Name=olcE {ECO:0000303|PubMed:30090271};
OS   Penicillium canescens.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5083;
RN   [1]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=30090271; DOI=10.1039/c5sc01965f;
RA   Yaegashi J., Romsdahl J., Chiang Y.M., Wang C.C.C.;
RT   "Genome mining and molecular characterization of the biosynthetic gene
RT   cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in Penicillium
RT   canescens.";
RL   Chem. Sci. 6:6537-6544(2015).
RN   [2]
RP   ERRATUM OF PUBMED:30090271.
RX   PubMed=30123464; DOI=10.1039/c6sc90012g;
RA   Yaegashi J., Romsdahl J., Chiang Y.M., Wang C.C.C.;
RT   "Correction: Genome mining and molecular characterization of the
RT   biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine
RT   B, in Penicillium canescens.";
RL   Chem. Sci. 7:2440-2440(2016).
CC   -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of 15-deoxyoxalicine B (PubMed:30090271). The
CC       first step of the pathway is the synthesis of nicotinyl-CoA from
CC       nicotinic acid by the nicotinic acid-CoA ligase olcI (PubMed:30090271).
CC       Nicotinyl-CoA is then a substrate of polyketide synthase olcA to
CC       produce 4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one (HPPO) which is
CC       further prenylated by the polyprenyl transferase olcH to yield
CC       geranylgeranyl-HPPO (PubMed:30090271). Geranylgeranyl pyrophosphate is
CC       provided by the cluster-specific geranylgeranyl pyrophosphate synthase
CC       olcC (PubMed:30090271). The FAD-dependent monooxygenase olcE catalyzes
CC       the epoxidation of geranylgeranyl-HPPO and the terpene cyclase olcD
CC       catalyzes the cyclization of the terpenoid component, resulting in the
CC       formation of the tricyclic terpene moiety seen in predecaturin E
CC       (PubMed:30090271). The cytochrome P450 monooxygenase then catalyzes the
CC       allylic oxidation of predecaturin E, which is followed by
CC       spirocylization with concomitant loss of one molecule of water to form
CC       decaturin E (PubMed:30090271). Decaturin E is the substrate of the
CC       cytochrome P450 monooxygenase olcJ which hydroxylates it at the C-29
CC       position to form decaturin F (PubMed:30090271). The short-chain
CC       dehydrogenase/reductase olcF may catalyze the oxidation of decaturin F
CC       to generate the 29-hydroxyl-27-one intermediate, and subsequent
CC       hemiacetal formation probably leads to the formation of decaturin C
CC       (Probable). The dioxygenase olcK may be a peroxisomal enzyme that
CC       catalyzes the hydroxylation of decaturin C into decaturin A once
CC       decaturin C is shuttled into the peroxisome by the MFS transporter olcL
CC       (Probable). Finally the cytochrome P450 monooxygenase olcB catalyzes
CC       the oxidative rearrangement to yield 15-deoxyoxalicine B
CC       (PubMed:30090271). In the absence of olcJ, decaturin E may be shunted
CC       to a pathway in which it is oxidized to a ketone, possibly by olcF, to
CC       form decaturin D, which undergoes further allylic oxidation to yield
CC       decaturin G (PubMed:30090271). Moreover, in the absence of oclK or
CC       oclL, oclB can convert decaturin C into 15-deoxyoxalicine A
CC       (PubMed:30090271). {ECO:0000269|PubMed:30090271,
CC       ECO:0000305|PubMed:30090271}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:30090271}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of 15-deoxyoxalicine B.
CC       {ECO:0000269|PubMed:30090271}.
CC   -!- MISCELLANEOUS: The 15-deoxyoxalicine B cluster is a rare cluster that
CC       contains its own geranylgeranyl pyrophosphate synthase (olcC), in
CC       contrast to other related clusters which rely on a FPP/GGPP synthase
CC       localized outside of the cluster. {ECO:0000269|PubMed:30090271}.
CC   -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC       {ECO:0000305}.
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DR   SMR; P9WEQ4; -.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Membrane; Monooxygenase; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..465
FT                   /note="FAD-dependent monooxygenase olcE"
FT                   /id="PRO_0000453891"
FT   TRANSMEM        9..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         36..37
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         131
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         308
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         318..322
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
SQ   SEQUENCE   465 AA;  52098 MW;  F32BAB655A457860 CRC64;
     MEPKDFKVII IGGSVAGLTL ALSLNKIGID YVVLEKRAHI APQEGASIGI LPHGGRILEQ
     LGLFEAVERS IEPLHTAHIR FPDGFEYTTA SPSVLNDRFG LPLAFLERQK MLQILFDAQT
     EKSKILCGKK VTKIEDFEES MTVYTEDGST YTGDLVVGAD GVHSQVRTEM WRLAEKMQPG
     IVSNTEKSSM TVQYTCVFGI SAAVPGLVPG EQVASFNDKR SFLTFPGKNG RVFWFLINRL
     DQEHSYSSAP RFSMKDTETI CHQFLEDIIY GDVRFNDLWS RKEVCSVTAL EEGAFRTWSY
     RRIVCIGDSM HKMAPNTGQG ANCAIEDVAA LANMLHACVV TTERHCKPTT KELSTLLEGY
     TKRRFHRIKK IYQASRLVVR LQARETLLLR MMGRYYIPRS GDVPADVASK MIAGAVALDF
     LPIPSRSGPG WISFKTMESR LRYWIVGGAI PVLLIMSMWL WQVVL