CDMF_TALVE
ID CDMF_TALVE Reviewed; 256 AA.
AC A0A3G9HAL8;
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=Short-chain dehydrogenase/reductase cdmF {ECO:0000303|PubMed:30417647};
DE EC=1.1.1.- {ECO:0000269|PubMed:30417647};
DE AltName: Full=chrodrimanin B biosynthesis cluster protein F {ECO:0000303|PubMed:30417647};
GN Name=cdmF {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: Short-chain dehydrogenase/reductase; part of the gene cluster
CC that mediates the biosynthesis of chrodrimanin B, a meroterpenoid that
CC acts 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 + A = AH2 + chrodrimanin C;
CC Xref=Rhea:RHEA:65264, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:156411, ChEBI:CHEBI:156412;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65265;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + chrodrimanin F = AH2 + chrodrimanin H;
CC Xref=Rhea:RHEA:65328, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:156415, ChEBI:CHEBI:156416;
CC Evidence={ECO:0000269|PubMed:30417647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65329;
CC Evidence={ECO:0000269|PubMed:30417647};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30417647}.
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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; LC422696; BBG28485.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3G9HAL8; -.
DR SMR; A0A3G9HAL8; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW NAD; NADP; Oxidoreductase.
FT CHAIN 1..256
FT /note="Short-chain dehydrogenase/reductase cdmF"
FT /id="PRO_0000449131"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 10..18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 34..35
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 157..161
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 256 AA; 26997 MW; D8AD23DDB45B4F32 CRC64;
MGLLQDYVII VTGSASGIGY ATSSTALREG AHVFGVDVSP LPADLCDHPN FQSFQGDLTE
DSTAQAVVTA CTQAFGNRID GLLNVAGVLD NFASVDAVTD QIWNKCLAVN LTAPVKLMRA
VIPIMRTQKR GSIVNVSSKA GISGGAAGVA YTASKHGLIG VTKNVAWRFK EENIRCNAVC
PGGVLTNIGS DIDRESFDME AFETMKPVQL AHMPDQSKGP RITPEEVAQV MIFLVSGLSS
KVNGAVIPVD DAWSTI
