SDNP_SORAA
ID SDNP_SORAA Reviewed; 272 AA.
AC A0A1B4XBI5;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 25-MAY-2022, entry version 6.
DE RecName: Full=Sordarin/hypoxysordarin biosynthesis cluster protein P {ECO:0000303|PubMed:27072286};
GN Name=sdnP {ECO:0000303|PubMed:27072286};
OS Sordaria araneosa (Pleurage araneosa).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Sordaria.
OX NCBI_TaxID=573841;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=ATCC 36386 / NRRL 3196;
RX PubMed=27072286; DOI=10.1038/ja.2016.40;
RA Kudo F., Matsuura Y., Hayashi T., Fukushima M., Eguchi T.;
RT "Genome mining of the sordarin biosynthetic gene cluster from Sordaria
RT araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and
RT GDP-6-deoxyaltrose transferase.";
RL J. Antibiot. 69:541-548(2016).
CC -!- FUNCTION: Part of the gene cluster that mediates the biosynthesis of
CC sordarin and hypoxysordarin, glycoside antibiotics with a unique
CC tetracyclic diterpene aglycone structure (PubMed:27072286). First, the
CC geranylgeranyl diphosphate synthase sdnC constructs GGDP from farnesyl
CC diphosphate and isopentenyl diphosphate (PubMed:27072286). The
CC diterpene cyclase sdnA then catalyzes the cyclization of GGDP to afford
CC cycloaraneosene (PubMed:27072286). Cycloaraneosene is then hydroxylated
CC four times by the putative cytochrome P450 monooxygenases sdnB, sdnE,
CC sdnF and sdnH to give a hydroxylated cycloaraneosene derivative such as
CC cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286). Although the order
CC of the hydroxylations is unclear, at least C8, C9 and C13 of the
CC cycloaraneosene skeleton are hydroxylated before the sordaricin
CC formation (PubMed:27072286). Dehydration of the 13-hydroxy group of the
CC hydroxylated cycloaraneosene derivative might be catalyzed by an
CC unassigned hypothetical protein such as sdnG and sdnP to construct the
CC cyclopentadiene moiety (PubMed:27072286). The FAD-dependent
CC oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the
CC hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-
CC Villiger oxidation to give the lactone intermediate (PubMed:27072286).
CC The presumed lactone intermediate would be hydrolyzed to give an
CC acrolein moiety and a carboxylate moiety (PubMed:27072286). Then,
CC [4+2]cycloaddition would occur between the acrolein moiety and the
CC cyclopentadiene moiety to give sordaricin (PubMed:27072286). SdnN might
CC also be involved in the [4+2]cycloaddition after the hypothesized
CC oxidation to accommodate the oxidized product and prompt the
CC [4+2]cycloaddition (PubMed:27072286). GDP-6-deoxy-D-altrose may be
CC biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-
CC dehydratase sdnI and the short-chain dehydrogenase sdnK
CC (PubMed:27072286). The glycosyltransferase sdnJ catalyzes the
CC attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin
CC to give 4'-O-demethylsordarin (PubMed:27072286). The methyltransferase
CC sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
CC Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
CC The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would
CC be constructed by an iterative type I PKS sdnO and the trans-acting
CC polyketide methyltransferase sdnL. SdnL would be responsible for the
CC introduction of an alpha-methyl group of the polyketide chain
CC (PubMed:27072286). Alternatively, the beta-lactamase-like protein sdnR
CC might be responsible for the cleavage and transfer of the polyketide
CC chain from the PKS sdnO to sordarin (PubMed:27072286). Two putative
CC cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the
CC epoxidations of the polyketide chain to complete the biosynthesis of
CC hypoxysordarin (PubMed:27072286). Transcriptional regulators sdnM and
CC sdnS are presumably encoded for the transcriptional regulation of the
CC expression of the sdn gene cluster (PubMed:27072286).
CC {ECO:0000269|PubMed:27072286}.
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:27072286}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
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DR EMBL; LC079035; BAV32160.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1B4XBI5; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Glycoprotein; Membrane; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..272
FT /note="Sordarin/hypoxysordarin biosynthesis cluster protein
FT P"
FT /id="PRO_0000441059"
FT TRANSMEM 31..51
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 67..87
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 272 AA; 30637 MW; AA81D478AE51CA76 CRC64;
MSSANNISGA PETGDFTFTQ HFNVSATPSE FLASIWPYRH MMWIGPMLLF LAPRFYNTLK
NTAFSRAYHM PYSILALHVF ISFVDLANYH TQVFLANGAI HPASQIDALI CIVQCWTSLY
ITAQHHLLPK IAMEVTRATF HCMSVQRLFA TAMAIRTGDP RWHEASIMLL NNFIWARLLI
AYCKMGRFSW KQRYGVGIVG SHLLGMWNGT YPHGIAIYCG LMVVLLNIDG WAKGRDSSVA
RALRYLGLAT PADWYIKVGI DPPTKSAEKK EA
