CDMA_TALVE
ID CDMA_TALVE Reviewed; 293 AA.
AC A0A3G9H185;
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 cdmA {ECO:0000303|PubMed:30417647};
DE EC=1.14.11.- {ECO:0000269|PubMed:30417647};
DE AltName: Full=Chrodrimanin B biosynthesis cluster protein A {ECO:0000303|PubMed:30417647};
GN Name=cdmA {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 + chrodrimanin C + O2 = CO2 + H2O + succinate +
CC verruculide A; Xref=Rhea:RHEA:65300, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:156412, ChEBI:CHEBI:156413;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65301;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + chrodrimanin H + O2 = chrodrimanin E + CO2 +
CC H2O + succinate; Xref=Rhea:RHEA:65316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:156416, ChEBI:CHEBI:156417;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65317;
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}.
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DR EMBL; LC422696; BBG28480.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3G9H185; -.
DR SMR; A0A3G9H185; -.
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..293
FT /note="Dioxygenase cdmA"
FT /id="PRO_0000449126"
FT BINDING 135
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 137
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 212
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
SQ SEQUENCE 293 AA; 32800 MW; 72DC01F674719552 CRC64;
MTKLPSDASA IKRVEANTSP EQVIELLKQD GVVVLKDFLD QATVQSFREE IKPAIDDFEG
GPNFNPDGVK VDIGRGTKHV ANLTAISKTY RHDILNNKWM HSILEPLFRP HFGDYWMNRG
SVLHIEPGEP AQNLHRDDIL YRVTKLRQPG DPDLMINILI AVTEFRDDNG ATRFVPGSHV
WDDTRGVPTP DQASSAALRP GDALLFVGSL WHGAGSNQSD AFRQGLLLCI HPCHFTPMES
HLHVPRTIVE SMTPQAQKMI GWRSGITQHD VPIWLAGDHK MEETMGLRSQ EVQ
