DPMPH_MACPH
ID DPMPH_MACPH Reviewed; 203 AA.
AC K2RU68;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Short chain dehydrogenase/reductase dpmpH {ECO:0000303|PubMed:32286350};
DE EC=1.1.1.- {ECO:0000269|PubMed:32286350};
DE AltName: Full=Diterpenoid pyrone biosynthesis cluster protein H {ECO:0000303|PubMed:32286350};
GN Name=dpmpH {ECO:0000303|PubMed:32286350}; ORFNames=MPH_09200;
OS Macrophomina phaseolina (strain MS6) (Charcoal rot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetes incertae sedis; Botryosphaeriales; Botryosphaeriaceae;
OC Macrophomina.
OX NCBI_TaxID=1126212;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MS6;
RX PubMed=22992219; DOI=10.1186/1471-2164-13-493;
RA Islam M.S., Haque M.S., Islam M.M., Emdad E.M., Halim A., Hossen Q.M.M.,
RA Hossain M.Z., Ahmed B., Rahim S., Rahman M.S., Alam M.M., Hou S., Wan X.,
RA Saito J.A., Alam M.;
RT "Tools to kill: Genome of one of the most destructive plant pathogenic
RT fungi Macrophomina phaseolina.";
RL BMC Genomics 13:493-493(2012).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOTECHNOLOGY.
RX PubMed=32286350; DOI=10.1038/s41467-020-15664-4;
RA Tsukada K., Shinki S., Kaneko A., Murakami K., Irie K., Murai M.,
RA Miyoshi H., Dan S., Kawaji K., Hayashi H., Kodama E.N., Hori A., Salim E.,
RA Kuraishi T., Hirata N., Kanda Y., Asai T.;
RT "Synthetic biology based construction of biological activity-related
RT library of fungal decalin-containing diterpenoid pyrones.";
RL Nat. Commun. 11:1830-1830(2020).
CC -!- FUNCTION: Short chain dehydrogenase/reductase; part of the gene cluster
CC that mediates the biosynthesis of diterpenoid pyrones
CC (PubMed:32286350). The first step of the pathway is the synthesis of
CC the alpha-pyrone moiety by the polyketide synthase dpmpA via
CC condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units
CC and 2 methylations (Probable). The alpha-pyrone is then combined with
CC geranylgeranyl pyrophosphate (GGPP) formed by the GGPP synthase dpmpD
CC through the action of the prenyltransferase dpmpC to yield a linear
CC alpha-pyrone diterpenoid (Probable). Subsequent steps in the
CC diterpenoid pyrone biosynthetic pathway involve the decalin core
CC formation, which is initiated by the epoxidation of the C10-C11 olefin
CC by the FAD-dependent oxidoreductase dpmpE, and is followed by a
CC cyclization cascade catalyzed by the terpene cyclase dpmpB (Probable).
CC The short chain dehydrogenase/reductase dpmpG then oxidizes the 8S
CC hydroxy group to a ketone and the short chain dehydrogenase/reductase
CC dpmpH reduces the ketone to the 8R hydroxy group to yield higginsianin
CC B (PubMed:32286350). Higginsianin B is further methylated by the
CC methyltransferase dpmpI to produce the intermediate named FDDP B
CC (PubMed:32286350). The cytochrome P450 monooxygenase dpmpJ then
CC oxidizes the C-26 methyl to primary alcohol, producing the final
CC diterpenoid pyrone with a C-26 primary alcohol on the gamma-pyrone
CC moiety named FDDP C (PubMed:32286350). {ECO:0000269|PubMed:32286350,
CC ECO:0000305|PubMed:32286350}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:32286350}.
CC -!- BIOTECHNOLOGY: Diterpenoid pyrones display various biological
CC activities and FDDP C shows anti-cancer and anti-HIV activities
CC (PubMed:32286350). FDDP C shows also inhibitory activity of 42-mer-
CC amyloid beta aggregation that is involved in the pathogenesis of
CC Alzheimer's disease (PubMed:32286350). {ECO:0000269|PubMed:32286350}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AHHD01000387; EKG13734.1; -; Genomic_DNA.
DR AlphaFoldDB; K2RU68; -.
DR EnsemblFungi; EKG13734; EKG13734; MPH_09200.
DR eggNOG; KOG1208; Eukaryota.
DR HOGENOM; CLU_1349169_0_0_1; -.
DR InParanoid; K2RU68; -.
DR OrthoDB; 921996at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007129; Unassembled WGS sequence.
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 SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..203
FT /note="Short chain dehydrogenase/reductase dpmpH"
FT /id="PRO_0000451552"
FT ACT_SITE 77
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 6..8
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 77..81
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 110..112
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 203 AA; 22081 MW; 717E3AB7F7BC9A1B CRC64;
MSAIGHSPTA CSRCSRPRLR RKDLTSVLSP RLPCFKVSSS GEAFATDKAD FITPKDLDDP
CASPGWEASS LAQAKRYGKS KMANVLFAAE LQRRMDAEGV DIISISLNPG PVKTQGAADV
LPFMVRPMVW LFFKDPAEGA QTTLFAAAAA EIREEKERWK GGYLDGPGKL KSPSPRARDP
QVAYNLWHTT ESAVRAIGVL DKS
