CDMD_TALVE
ID CDMD_TALVE Reviewed; 307 AA.
AC A0A3G9GR23;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Dioxygenase cdmD {ECO:0000303|PubMed:30417647};
DE EC=1.14.11.- {ECO:0000269|PubMed:30417647};
DE AltName: Full=chrodrimanin B biosynthesis cluster protein D {ECO:0000303|PubMed:30417647};
GN Name=cdmD {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: Dioxygenase; part of the gene cluster that mediates the
CC biosynthesis of chrodrimanin B, a meroterpenoid that acts as a potent
CC blocker of insect GABA-gated chloride channels (PubMed:30417647). The
CC first step of the pathway is the biosynthesis of 6-hydroxymellein by
CC the polyketide synthase cdmE (PubMed:30417647). The prenyltransferase
CC cdmH acts as a 6-hydroxymellein 5-farnesyltransferase and produces the
CC hydrophobic metabolite verruculide C (PubMed:30417647). The FAD-
CC dependent monooxygenase cdmI further converts verruculide C into
CC verruculide B (PubMed:30417647). The terpene cyclase cdmG then produced
CC the pentacyclic molecule 3-hydroxypentacecilide A, the backbone
CC structure of chrodrimanin B, via folding the farnesyl moiety of the
CC substrate into the chair-boat conformation (PubMed:30417647). The
CC short-chain dehydrogenase/reductase cdmF functions as the 3-OH
CC dehydrogenase that oxidizes the C-3 hydroxyl group of 3-
CC hydroxypentacecilide A and produces chrodrimanin C, the dehydrogenated
CC product of 3-hydroxypentacecilide A (PubMed:30417647). The cytochrome
CC P450 monooxygenase cdmJ then accepts both 3-hydroxypentacecilide A and
CC chrodrimanin C and functions as a C-7-beta-hydroxylase to produce
CC respectively chrodrimanin H and chrodrimanin F (PubMed:30417647). The
CC dioxygenase cdmA accepts chrodrimanin H to afford chrodrimanin E, which
CC is further transformed to chrodrimanin A by the dioxygenase cdmD
CC (PubMed:30417647). CdmA can also accept chrodrimanin C as substrate to
CC convert it into verruculide A, which is further converted into
CC chrodrimanin T by cdmD (PubMed:30417647). The last step of the
CC biosynthesis is proposed to be performed by the acetyltransferase cdmC
CC which acetylates chrodrimanin A to yield chrodrimanin B (Probable). The
CC pathway may also lead to the production of additional shunt products,
CC including chrodrimanins T and U (PubMed:30417647).
CC {ECO:0000269|PubMed:30417647, ECO:0000305|PubMed:30417647}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + verruculide A = chrodrimanin T + CO2 +
CC succinate; Xref=Rhea:RHEA:65304, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:156413, ChEBI:CHEBI:156414;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65305;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + chrodrimanin E + O2 = chrodrimanin A + CO2 +
CC succinate; Xref=Rhea:RHEA:65320, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:156417, ChEBI:CHEBI:156418;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65321;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:A0A097ZPD9};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30417647}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
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 PhyH 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; LC422696; BBG28483.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3G9GR23; -.
DR SMR; A0A3G9GR23; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..307
FT /note="Dioxygenase cdmD"
FT /id="PRO_0000449127"
FT BINDING 146
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 148
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 226
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
SQ SEQUENCE 307 AA; 35255 MW; 2DFBAD6C0CAC703C CRC64;
MTVTINKSSV PHKVDFATPL SDVICHIKED GAVIVRGFMD VETIQKLQEE VDTAVEKGSF
GPRYQEYNEE AGEIPKHEIY KRGEGKKTKH MKNLALTSET FRNDVLNHKW MHAVCEQIYG
EEFGDYWMNC AHILHLEPGE KAQFFHRDTG VYRVSDFRRR LNDPEFMINF LVSLTEFRED
NGATQLIPGS HKWDAAHPPT FYGSDEAVPA ILEPGDAVVY LGSLFHGAGE NRSLDYRRGM
IVSMHPAHFT PMESHFHLPK EIVESMTPLA QQMVGWRTMN NQNKIPIWQA GDDKIEDVLR
LQHKEVY
