CDMJ_TALVE
ID CDMJ_TALVE Reviewed; 517 AA.
AC A0A3G9GNK2;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Cytochrome P450 monooxygenase cdmJ {ECO:0000303|PubMed:30417647};
DE EC=1.-.-.- {ECO:0000269|PubMed:30417647};
DE AltName: Full=chrodrimanin B biosynthesis cluster protein J {ECO:0000303|PubMed:30417647};
GN Name=cdmJ {ECO:0000303|PubMed:30417647};
OS Talaromyces verruculosus (Penicillium verruculosum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Talaromyces.
OX NCBI_TaxID=198730;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=TPU1311;
RX PubMed=30417647; DOI=10.1021/acs.orglett.8b03268;
RA Bai T., Quan Z., Zhai R., Awakawa T., Matsuda Y., Abe I.;
RT "Elucidation and heterologous reconstitution of chrodrimanin B
RT biosynthesis.";
RL Org. Lett. 20:7504-7508(2018).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=26115570; DOI=10.1016/j.bmcl.2015.06.026;
RA Yamazaki H., Nakayama W., Takahashi O., Kirikoshi R., Izumikawa Y.,
RA Iwasaki K., Toraiwa K., Ukai K., Rotinsulu H., Wewengkang D.S.,
RA Sumilat D.A., Mangindaan R.E., Namikoshi M.;
RT "Verruculides A and B, two new protein tyrosine phosphatase 1B inhibitors
RT from an Indonesian ascidian-derived Penicillium verruculosum.";
RL Bioorg. Med. Chem. Lett. 25:3087-3090(2015).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=25902139; DOI=10.1371/journal.pone.0122629;
RA Xu Y., Furutani S., Ihara M., Ling Y., Yang X., Kai K., Hayashi H.,
RA Matsuda K.;
RT "Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect
RT GABA-Gated Chloride Channels.";
RL PLoS ONE 10:E0122629-E0122629(2015).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of chrodrimanin B, a meroterpenoid that acts
CC as a potent blocker of insect GABA-gated chloride channels
CC (PubMed:30417647). The first step of the pathway is the biosynthesis of
CC 6-hydroxymellein by the polyketide synthase cdmE (PubMed:30417647). The
CC prenyltransferase cdmH acts as a 6-hydroxymellein 5-farnesyltransferase
CC and produces the hydrophobic metabolite verruculide C
CC (PubMed:30417647). The FAD-dependent monooxygenase cdmI further
CC converts verruculide C into verruculide B (PubMed:30417647). The
CC terpene cyclase cdmG then produced the pentacyclic molecule 3-
CC hydroxypentacecilide A, the backbone structure of chrodrimanin B, via
CC folding the farnesyl moiety of the substrate into the chair-boat
CC conformation (PubMed:30417647). The short-chain dehydrogenase/reductase
CC cdmF functions as the 3-OH dehydrogenase that oxidizes the C-3 hydroxyl
CC group of 3-hydroxypentacecilide A and produces chrodrimanin C, the
CC dehydrogenated product of 3-hydroxypentacecilide A (PubMed:30417647).
CC The cytochrome P450 monooxygenase cdmJ then accepts both 3-
CC hydroxypentacecilide A and chrodrimanin C and functions as a C-7-beta-
CC hydroxylase to produce respectively chrodrimanin H and chrodrimanin F
CC (PubMed:30417647). The dioxygenase cdmA accepts chrodrimanin H to
CC afford chrodrimanin E, which is further transformed to chrodrimanin A
CC by the dioxygenase cdmD (PubMed:30417647). CdmA can also accept
CC chrodrimanin C as substrate to convert it into verruculide A, which is
CC further converted into chrodrimanin T by cdmD (PubMed:30417647). The
CC last step of the biosynthesis is proposed to be performed by the
CC acetyltransferase cdmC which acetylates chrodrimanin A to yield
CC chrodrimanin B (Probable). The pathway may also lead to the production
CC of additional shunt products, including chrodrimanins T and U
CC (PubMed:30417647). {ECO:0000269|PubMed:30417647,
CC ECO:0000305|PubMed:30417647}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxypentacecilide A + H(+) + NADPH + O2 = chrodrimanin F
CC + H2O + NADP(+); Xref=Rhea:RHEA:65268, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:156411, ChEBI:CHEBI:156415;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65269;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chrodrimanin C + H(+) + NADPH + O2 = chrodrimanin H + H2O +
CC NADP(+); Xref=Rhea:RHEA:65272, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:156412, ChEBI:CHEBI:156416;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65273;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + verruculide A = chrodrimanin E + H2O +
CC NADP(+); Xref=Rhea:RHEA:65332, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:156413, ChEBI:CHEBI:156417;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65333;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chrodrimanin T + H(+) + NADPH + O2 = chrodrimanin A + H2O +
CC NADP(+); Xref=Rhea:RHEA:65336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:156414, ChEBI:CHEBI:156418;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65337;
CC Evidence={ECO:0000269|PubMed:30417647};
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:30417647}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Compounds in the chrodrimanin family such as
CC chrodrimanin A or verruculide A exhibit strong inhibitory activities
CC against protein tyrosine phosphatase 1B (PTP1B) and therefore, they
CC could potentially be developed into drugs for the treatment of type 2
CC diabetes or obesity (PubMed:26115570). Furthermore, chrodrimanin B, the
CC end product of the pathway involving chrodrimanin A or verruculide A,
CC does not exhibit the PTP1B inhibitory activity, while it functions as a
CC potent blocker of insect GABA-gated chloride channels
CC (PubMed:25902139). {ECO:0000269|PubMed:25902139,
CC ECO:0000269|PubMed:26115570}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; LC422696; BBG28489.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3G9GNK2; -.
DR SMR; A0A3G9GNK2; -.
DR UniPathway; UPA00213; -.
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; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..517
FT /note="Cytochrome P450 monooxygenase cdmJ"
FT /id="PRO_0000449135"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 451
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"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 517 AA; 58460 MW; BA147392914408C3 CRC64;
MLSEDLATSF LPPSYMWSLT LFALCLSAIL MFPFLTGRRL SITHRKQGWR ISLVNTRGDF
QNEAEQLIRM GFSKSPSAFR MSTDGGPRLI LSQKHLDAMS DDDHFNVAEA VKRDYLLDLF
GFETAFHGTL HSEIVAPAVT AMTKKLVPLV PLMSKEAALG LEKEWTDNSE YHDVPLQPTL
GGVVARLASL AFVGPDLCRN PTWLEITVSY TINRVIAVYV LRIFPSFLQP FVHWVLPPCR
KLRAQIQQAR ELILPALKHE RQLQSAGNAK RDPNRPFSSL AWNDEYAAGR LYDPTVAQLR
MIFVSIHTTI DMAVKVLVRL CEHPELIQPL REEIVTVCGE NGLTHSSLER LLLMDSLMKE
TQRLEPASLA TIARYTHRKT TLSDGTIVPK GTQVVLPNMF MWNNESIYPD SNTFDAYRFL
RMRDDPETAK LASFTRSSHI HTAFGHGKHT CPGRFFASDT IKIILCHILL KYDLQLCDGE
APAKKRYGFA MYRDPDARIR VRRRGVEGVS EGILAGF
