CDMH_TALVE
ID CDMH_TALVE Reviewed; 325 AA.
AC A0A3G9GNJ4;
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=6-hydroxymellein 5-farnesyltransferase cdmH {ECO:0000303|PubMed:30417647};
DE AltName: Full=Polyprenyl transferase cdmH {ECO:0000303|PubMed:30417647};
DE EC=2.5.1.- {ECO:0000269|PubMed:30417647};
DE AltName: Full=chrodrimanin B biosynthesis cluster protein H {ECO:0000303|PubMed:30417647};
GN Name=cdmH {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: 6-hydroxymellein 5-farnesyltransferase; part of the gene
CC cluster that mediates the biosynthesis of chrodrimanin B, a
CC meroterpenoid that acts as a potent blocker of insect GABA-gated
CC chloride channels (PubMed:30417647). The first step of the pathway is
CC the biosynthesis of 6-hydroxymellein by the polyketide synthase cdmE
CC (PubMed:30417647). The prenyltransferase cdmH acts as a 6-
CC hydroxymellein 5-farnesyltransferase and produces the hydrophobic
CC metabolite verruculide C (PubMed:30417647). The FAD-dependent
CC monooxygenase cdmI further converts verruculide C into verruculide B
CC (PubMed:30417647). The terpene cyclase cdmG then produced the
CC pentacyclic molecule 3-hydroxypentacecilide A, the backbone structure
CC of chrodrimanin B, via folding the farnesyl moiety of the substrate
CC into the chair-boat conformation (PubMed:30417647). The short-chain
CC dehydrogenase/reductase cdmF functions as the 3-OH dehydrogenase that
CC oxidizes the C-3 hydroxyl group of 3-hydroxypentacecilide A and
CC produces chrodrimanin C, the dehydrogenated product of 3-
CC hydroxypentacecilide A (PubMed:30417647). The cytochrome P450
CC 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=(2E,6E)-farnesyl diphosphate + 6-hydroxymellein = diphosphate
CC + verruculide C; Xref=Rhea:RHEA:65252, ChEBI:CHEBI:16368,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:156409, ChEBI:CHEBI:175763;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65253;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P32378};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30417647}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-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 UbiA prenyltransferase family.
CC {ECO:0000305}.
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DR EMBL; LC422696; BBG28487.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3G9GNJ4; -.
DR SMR; A0A3G9GNJ4; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016765; F:transferase activity, transferring alkyl or aryl (other than methyl) groups; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.357.140; -; 1.
DR InterPro; IPR039653; Prenyltransferase.
DR InterPro; IPR000537; UbiA_prenyltransferase.
DR InterPro; IPR030470; UbiA_prenylTrfase_CS.
DR InterPro; IPR044878; UbiA_sf.
DR PANTHER; PTHR11048; PTHR11048; 1.
DR Pfam; PF01040; UbiA; 1.
DR PROSITE; PS00943; UBIA; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Magnesium; Membrane; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..325
FT /note="6-hydroxymellein 5-farnesyltransferase cdmH"
FT /id="PRO_0000449133"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 325 AA; 36377 MW; D1F2BF5DCEDFA9EE CRC64;
MAVLKQPQHH HGKHGGRSFY QLIAYLMLTS RLDNYGMLFT SFGGAGIYKS QDYTSTTSQA
SILRLAGLCT AHCVLLGAAG NTWNDWMDRD IDSKVARTKD RPLASGKISS GEAFTWMAFL
YSTSVGMLKA MLGDRNVWPF MVPLTAIILV YPLGKRPIAR KLRIYPQYLL GIAVGYPTMY
GWAAVYGPCM PISEILHRCV PLWIFLFFWS FYANTSYSYQ DVEDDRKMKV NSAYNLAGKR
IRALLAILAS IALSTIPFVL RPFSSAWLWL SWVGAWVPGI IQQLLSFDPS KPESGGVLHL
STVKLGLWTV FACTLELYLS NRAVI
