PRHI_PENBI
ID PRHI_PENBI Reviewed; 257 AA.
AC A0A1E1FFP5;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Short chain dehydrogenase prhI {ECO:0000303|PubMed:27602587};
DE EC=1.1.1.- {ECO:0000269|PubMed:27602587};
DE AltName: Full=Paraherquonin biosynthesis cluster protein I {ECO:0000303|PubMed:27602587};
GN Name=prhI {ECO:0000303|PubMed:27602587};
OS Penicillium brasilianum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=104259;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=ATCC 22354 / NBRC 6234 / CBS 338.59 / FRR 3454 / IMI 68220;
RX PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA Zhang H., Hayashi F., Abe I.;
RT "Discovery of key dioxygenases that diverged the paraherquonin and
RT acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL J. Am. Chem. Soc. 138:12671-12677(2016).
RN [2]
RP FUNCTION.
RX PubMed=28759016; DOI=10.1038/nchembio.2443;
RA Mori T., Iwabuchi T., Hoshino S., Wang H., Matsuda Y., Abe I.;
RT "Molecular basis for the unusual ring reconstruction in fungal
RT meroterpenoid biogenesis.";
RL Nat. Chem. Biol. 13:1066-1073(2017).
RN [3]
RP FUNCTION.
RX PubMed=29317628; DOI=10.1038/s41467-017-02371-w;
RA Nakashima Y., Mori T., Nakamura H., Awakawa T., Hoshino S., Senda M.,
RA Senda T., Abe I.;
RT "Structure function and engineering of multifunctional non-heme iron
RT dependent oxygenases in fungal meroterpenoid biosynthesis.";
RL Nat. Commun. 9:104-104(2018).
CC -!- FUNCTION: Short chain dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of paraherquonin, a meroterpenoid with a
CC unique, highly congested hexacyclic molecular architecture
CC (PubMed:27602587). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase prhL (By
CC similarity). Synthesis of DMOA is followed by farnesylation by the
CC prenyltransferase prhE, methylesterification by the methyl-transferase
CC prhM, epoxidation of the prenyl chain by the flavin-dependent
CC monooxygenase prhF, and cyclization of the farnesyl moiety by the
CC terpene cyclase prhH, to yield the tetracyclic intermediate,
CC protoaustinoid A (By similarity). The short chain dehydrogenase prhI
CC then oxidizes the C-3 alcohol group of the terpene cyclase product to
CC transform protoaustinoid A into protoaustinoid B (PubMed:27602587). The
CC FAD-binding monooxygenase prhJ catalyzes the oxidation of
CC protoaustinoid B into preaustinoid A which is further oxidized into
CC preaustinoid A1 by FAD-binding monooxygenase phrK (PubMed:27602587).
CC Finally, prhA leads to berkeleydione via the berkeleyone B intermediate
CC (PubMed:27602587, PubMed:29317628). PrhA is a multifunctional
CC dioxygenase that first desaturates at C5-C6 to form berkeleyone B,
CC followed by rearrangement of the A/B-ring to form the cycloheptadiene
CC moiety in berkeleydione (PubMed:27602587, PubMed:29317628).
CC Berkeleydione serves as the key intermediate for the biosynthesis of
CC paraherquonin as well as many other meroterpenoids (Probable). The
CC cytochrome P450 monooxygenases prhB, prhD, and prhN, as well as the
CC isomerase prhC, are probably involved in the late stage of
CC paraherquonin biosynthesis, after the production of berkeleydione
CC (Probable). Especially prhC might be a multifunctional enzyme that
CC catalyzes the D-ring expansion via intramolecular methoxy
CC rearrangement, as well as the hydrolysis of the expanded D-ring
CC (Probable). {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:27602587,
CC ECO:0000269|PubMed:29317628, ECO:0000305|PubMed:27602587,
CC ECO:0000305|PubMed:28759016, ECO:0000305|PubMed:29317628}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + protoaustinoid A = AH2 + protoaustinoid B;
CC Xref=Rhea:RHEA:65176, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:156350, ChEBI:CHEBI:156380;
CC Evidence={ECO:0000269|PubMed:27602587};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65177;
CC Evidence={ECO:0000269|PubMed:27602587};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27602587}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; LC127182; BAV69310.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1E1FFP5; -.
DR SMR; A0A1E1FFP5; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; NAD; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..257
FT /note="Short chain dehydrogenase prhI"
FT /id="PRO_0000449184"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255"
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 37..38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 56..58
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 138
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 151..155
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 184..187
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 257 AA; 26827 MW; 572BF47B16C32DAE CRC64;
MYNIQDHVVI ITGSSSGIGL AASTLALASG AKVFGIDISN SPTSVTANPN YTFFAADLSH
PESAKKAIAA CIAAYGNRID GLLNIAGVMD LNQSADTVTD DMWDRCIAIN LTAPVKLMRE
VIPIMRLRGK GSIVNVGSKA SMSGAVSGIA YTASKHGLVG ATKNVAWRFK HEGIRCNIVC
PGGVAATGIR DGVDSTQFDS EALEMMSVIH QAHASDHAKG LGLQPEDLAH SLLYFLSDLS
KGISGAVIPV DNAWSTI
