CYPL8_GANLU
ID CYPL8_GANLU Reviewed; 547 AA.
AC A0A2R4SBW0;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2018, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Ganoderic acid synthetase CYP5150L8 {ECO:0000303|PubMed:29476632};
DE EC=1.-.-.- {ECO:0000269|PubMed:29476632};
DE AltName: Full=Cytochrome P450 monooxygenase CYP5150L8 {ECO:0000303|PubMed:29476632};
GN Name=CYP5150L8 {ECO:0000303|PubMed:29476632};
OS Ganoderma lucidum (Ling zhi medicinal fungus) (Bracket fungus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Polyporales; Polyporaceae; Ganoderma.
OX NCBI_TaxID=5315;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=260125-1;
RA Cai P.;
RT "Production of Ganoderic acid Z in engineered yeast.";
RL Submitted (MAY-2017) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=29476632; DOI=10.1002/bit.26583;
RA Wang W.F., Xiao H., Zhong J.J.;
RT "Biosynthesis of a ganoderic acid in Saccharomyces cerevisiae by expressing
RT a cytochrome P450 gene from Ganoderma lucidum.";
RL Biotechnol. Bioeng. 115:1842-1854(2018).
RN [3]
RP FUNCTION, AND PATHWAY.
RX PubMed=31449331; DOI=10.1002/bit.27154;
RA Lan X., Yuan W., Wang M., Xiao H.;
RT "Efficient biosynthesis of antitumor ganoderic acid HLDOA using a dual
RT tunable system for optimizing the expression of CYP5150L8 and a Ganoderma
RT P450 reductase.";
RL Biotechnol. Bioeng. 116:3301-3311(2019).
RN [4]
RP INDUCTION.
RX PubMed=30821132; DOI=10.1111/1751-7915.13381;
RA Xu J.W., Yue T.H., Yu X., Zhao P., Li T., Li N.;
RT "Enhanced production of individual ganoderic acids by integrating
RT Vitreoscilla haemoglobin expression and calcium ion induction in liquid
RT static cultures of Ganoderma lingzhi.";
RL Microb. Biotechnol. 12:1180-1187(2019).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31865439; DOI=10.1007/s00253-019-10298-z;
RA Wang P.A., Xiao H., Zhong J.J.;
RT "CRISPR-Cas9 assisted functional gene editing in the mushroom Ganoderma
RT lucidum.";
RL Appl. Microbiol. Biotechnol. 104:1661-1671(2020).
CC -!- FUNCTION: Cytochrome P450 monoxygenase that is involved in the
CC biosynthesis of ganoderic acids (GA), a group of highly oxygenated
CC lanostane-type triterpenoids which well recognized as a main group of
CC unique bioactive compounds in the medicinal mushroom Ganoderma lucidum
CC (PubMed:29476632, PubMed:31449331, PubMed:31865439). CYP5150L8 alone is
CC able to catalyze the three-step oxidations at C-26 from lanosterol to
CC 3-hydroxy-lanosta-8,24-dien-26-oic acid (also called ganoderic acid Z
CC or HLDOA) (PubMed:29476632). The methyl group of lanosterol at C-26 is
CC first oxidized into hydroxyl group to form 3-hydroxy-lanosta-8,24-dien-
CC 26-ol (HLDO) (PubMed:29476632). The hydroxyl group at C-26 of HLDO is
CC further converted into a formyl group to form 3-hydroxy-lanosta-8,24-
CC dien-26-al (HLDA) (PubMed:29476632). Finally, the formyl group is
CC oxidized into a carboxyl group to produce 3-hydroxy-lanosta-8,24-dien-
CC 26-oic acid (HLDOA) (PubMed:29476632). {ECO:0000269|PubMed:29476632,
CC ECO:0000269|PubMed:31449331, ECO:0000269|PubMed:31865439}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 26-
CC hydroxylanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:68720, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16521, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:178023; Evidence={ECO:0000269|PubMed:29476632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68721;
CC Evidence={ECO:0000269|PubMed:29476632};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=26-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 26-oxolanosterol + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:68724, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:178023, ChEBI:CHEBI:178024;
CC Evidence={ECO:0000269|PubMed:29476632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68725;
CC Evidence={ECO:0000269|PubMed:29476632};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=26-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 3beta-hydroxy-lanosta-8, 24-dien-26-oate + 2 H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68728, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:178024, ChEBI:CHEBI:178025;
CC Evidence={ECO:0000269|PubMed:29476632};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68729;
CC Evidence={ECO:0000269|PubMed:29476632};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29476632, ECO:0000269|PubMed:31449331}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced in ganoderic acid (GA) producing
CC conditions. {ECO:0000269|PubMed:30821132}.
CC -!- DISRUPTION PHENOTYPE: Leads to a significant decrease in the titer of
CC the 4 ganoderic acids Mk, T, S and Me. {ECO:0000269|PubMed:31865439}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MF175172; AVZ44872.1; -; mRNA.
DR SMR; A0A2R4SBW0; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..547
FT /note="Ganoderic acid synthetase CYP5150L8"
FT /id="PRO_0000454388"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 487
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 547 AA; 61831 MW; EEC07BF0CA5FD115 CRC64;
MPDSSLVLVA IAGAAYIFWL VFHRYLVRSP LDNLPSPPSS PFLGNLPDII HRQSHLWWRH
VSNTYGPATK LTAFFGIQML YTFDPKAMYS ILVKDTELYP KKTAAYDDFT LFIGPGLLFA
EGAQHRRQRK WLNPVFSVAQ LRDVSHVFYG VAYKLEEAIR NRVGAQSQNL DVNGWMARTT
LEMLGQAGLG YSFDKFTEDS TDSYGEALKS FFPVINHVPL LNLFVMTLAN HIPKWLMRRV
LRLAVPFPHV LRLLRISETM QKRSSEIIQQ KKTALQKGDK ALIHQVGEGK DIMSVLLKSN
MNAPSDSEKL PDEELLAQMS TFILAGMDTT SNALSRILHL LAEHPDVQEK LRHELSEARE
IVGNGKDVPY DDLVKLPYLD AVCRETLRLH PPLNLIGRRA AKDMVVPLSS PVRGRDGTLV
NEVTLPKDTF VLLGLQACNT NKKLWGEDAY EWKPERWLQP LPSMLEEARV PGVYSNLMSF
SGGVRSCIGF KFSQLEMKVL LTILLPAFSF ELTEKPIFWN TSAVSYPTMD KDSTRPEMLL
KVKALAC
