ID BOT1_BOTFU Reviewed; 510 AA.
AC Q6WP49;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 08-MAY-2019, entry version 68.
DE RecName: Full=Cytochrome P450 monooxygenase BOT1 {ECO:0000303|PubMed:19035644};
DE EC=1.-.-.- {ECO:0000269|PubMed:15986930};
DE AltName: Full=Botrydial biosynthesis cluster protein 1 {ECO:0000303|PubMed:19035644};
DE AltName: Full=Calcineurin-dependent protein 5 {ECO:0000303|PubMed:14651630};
GN Name=BOT1 {ECO:0000303|PubMed:19035644};
GN Synonyms=CND5 {ECO:0000303|PubMed:14651630},
GN P450-12 {ECO:0000303|PubMed:15986930};
OS Botryotinia fuckeliana (Noble rot fungus) (Botrytis cinerea).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC Helotiales; Sclerotiniaceae; Botrytis.
OX NCBI_TaxID=40559 {ECO:0000312|EMBL:AAQ16576.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RC STRAIN=T4;
RX PubMed=14651630; DOI=10.1046/j.1365-2958.2003.03798.x;
RA Viaud M., Brunet-Simon A., Brygoo Y., Pradier J.-M., Levis C.;
RT "Cyclophilin A and calcineurin functions investigated by gene
RT inactivation, cyclosporin A inhibition and cDNA arrays approaches in
RT the phytopathogenic fungus Botrytis cinerea.";
RL Mol. Microbiol. 50:1451-1465(2003).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15986930; DOI=10.1094/MPMI-18-0602;
RA Siewers V., Viaud M., Jimenez-Teja D., Collado I.G., Gronover C.S.,
RA Pradier J.M., Tudzynski B., Tudzynski P.;
RT "Functional analysis of the cytochrome P450 monooxygenase gene bcbot1
RT of Botrytis cinerea indicates that botrydial is a strain-specific
RT virulence factor.";
RL Mol. Plant Microbe Interact. 18:602-612(2005).
RN [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=19035644; DOI=10.1021/cb800225v;
RA Pinedo C., Wang C.M., Pradier J.M., Dalmais B., Choquer M.,
RA Le Pecheur P., Morgant G., Collado I.G., Cane D.E., Viaud M.;
RT "Sesquiterpene synthase from the botrydial biosynthetic gene cluster
RT of the phytopathogen Botrytis cinerea.";
RL ACS Chem. Biol. 3:791-801(2008).
RN [4]
RP FUNCTION.
RX PubMed=19476353; DOI=10.1021/ja9021649;
RA Wang C.M., Hopsn R., Lin X., Cane D.E.;
RT "Biosynthesis of the sesquiterpene botrydial in Botrytis cinerea.
RT Mechanism and stereochemistry of the enzymatic formation of
RT presilphiperfolan-8beta-ol.";
RL J. Am. Chem. Soc. 131:8360-8361(2009).
RN [5]
RP FUNCTION.
RX PubMed=27529428; DOI=10.1021/acschembio.6b00581;
RA Moraga J., Dalmais B., Izquierdo-Bueno I., Aleu J., Hanson J.R.,
RA Hernandez-Galan R., Viaud M., Collado I.G.;
RT "Genetic and molecular basis of botrydial biosynthesis: connecting
RT cytochrome P450-encoding genes to biosynthetic intermediates.";
RL ACS Chem. Biol. 11:2838-2846(2016).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=27721016; DOI=10.1016/j.fgb.2016.10.003;
RA Porquier A., Morgant G., Moraga J., Dalmais B., Luyten I., Simon A.,
RA Pradier J.M., Amselem J., Collado I.G., Viaud M.;
RT "The botrydial biosynthetic gene cluster of Botrytis cinerea displays
RT a bipartite genomic structure and is positively regulated by the
RT putative Zn(II)2Cys6 transcription factor BcBot6.";
RL Fungal Genet. Biol. 96:33-46(2016).
RN [7]
RP FUNCTION.
RX PubMed=28617493; DOI=10.1039/c7ob01088e;
RA Franco Dos Santos G., Moraga J., Takahashi J.A., Viaud M.,
RA Hanson J.R., Hernandez Galan R., Collado I.G.;
RT "The formation of sesquiterpenoid presilphiperfolane and cameroonane
RT metabolites in the Bcbot4 null mutant of Botrytis cinerea.";
RL Org. Biomol. Chem. 15:5357-5363(2017).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster
CC that mediates the biosynthesis of botrydial (PubMed:14651630,
CC PubMed:15986930). Botrydial is necessary for colonization of plant
CC tissue by the T4 strain (PubMed:19035644). It is a strain-
CC dependent virulence factor since highly aggressive strains like
CC SAS56 or B05 still retain substantial virulence when botrydial
CC synthesis is impaired, since they produce also botcinic acid
CC (PubMed:15986930). The first step of botrydial biosynthesis is
CC performed by the sesquiterpene synthase BOT2 which catalyzes the
CC cyclization of farnesyl diphosphate (FPP) to presilphiperfolan-8-
CC beta-ol (PSP) (PubMed:19035644, PubMed:19476353). The cytochrome
CC P450 monooxygenase BOT4 then catalyzes the hydroxylation at C-4 to
CC give a probotryane intermediate (PubMed:27529428,
CC PubMed:28617493). Acetylation of the hydroxyl at C-4 is carried
CC out by the acetyltransferase BOT5, followed by the combined action
CC of the P450 monooxygenases BOT3 and BOT1, to yield finally the
CC glycol, via the regio- and stereospecific hydroxylations at C-10
CC and C-15 of the probotryane intermediates, respectively
CC (PubMed:15986930, PubMed:27529428). The cleavage of the C10-C15
CC bond of probotryane skeleton is an intriguing and chemically
CC important reaction, which could be mediated by some of the
CC monooxygenases or by a combination of them (PubMed:27529428). It
CC is possible that either BOT3 or BOT1 would oxidize either the
CC 10- or the 15-hydroxy group to the hydroperoxide derivative, which
CC would then undergo heterolytic fragmentation to give the
CC dialdehyde botrydial (PubMed:27529428). Finally, the dehydrogenase
CC BOT7 might be involved in the conversion of botrydial to
CC dihydrobotrydial (PubMed:27721016). {ECO:0000269|PubMed:14651630,
CC ECO:0000269|PubMed:15986930, ECO:0000269|PubMed:19035644,
CC ECO:0000269|PubMed:19476353, ECO:0000269|PubMed:27529428,
CC ECO:0000269|PubMed:27721016, ECO:0000269|PubMed:28617493}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:15986930}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: The botrydial biosynthesis cluster genes are co-
CC regulated by the Ca(2+)/calcineurin signal transduction pathway,
CC which is under the control of the alpha subunit BCG1 of a
CC heterotrimeric G protein (PubMed:14651630, PubMed:19035644).
CC Expression of the cluster is also positively regulated by the
CC cluster-specific transcription factor BOT6 (PubMed:27721016).
CC {ECO:0000269|PubMed:14651630, ECO:0000269|PubMed:19035644,
CC ECO:0000269|PubMed:27721016}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of 10-beta,15-
CC alpha-dihydroxyprobotryane, botrydial, and of some of its
CC relatives (PubMed:15986930). {ECO:0000269|PubMed:15986930}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AY277723; AAQ16576.1; -; Genomic_DNA.
DR eggNOG; KOG0156; Eukaryota.
DR eggNOG; COG2124; LUCA.
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:0009405; P:pathogenesis; IEA:UniProtKB-KW.
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 Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1 510 Cytochrome P450 monooxygenase BOT1.
FT /FTId=PRO_0000444642.
FT TRANSMEM 16 36 Helical. {ECO:0000255}.
FT METAL 454 454 Iron (heme axial ligand).
FT {ECO:0000250|UniProtKB:P04798}.
FT CARBOHYD 476 476 N-linked (GlcNAc...) asparagine.
FT {ECO:0000255|PROSITE-ProRule:PRU00498}.
SQ SEQUENCE 510 AA; 58162 MW; A591F786FC5D565C CRC64;
MGLLSDVINN FLPETPLAWA ALILASFTLY SVQLVVRRLY FHPLSKIPGP FLARSRYWYE
FYQDIILGGI YVKNYAALHE KYGPVLRASP DRVHVSDPDF FHEVYSSGSK YMKDPAFFQA
AGGIPEALPA IVDVEYHRRR RKLINDLFSA KSMEALSHLV LKVVQNALSK AHEHHEANKV
LDIQRLYTGI TIDTIMQVLC DRTLNFIDAK EEEEPPFLAT LRTFSENFFL LKHFPILIWM
ALNIPKSIAQ KLIPGEFEFR ASINQWIRDR ASEHELGVEK AEDGRKTVID LLLRPEDGGR
PLTHQAVEDE TYSFAFAGTH TTSHTMSMGT YYLLSHPAKL QKLRDELKPI PKNDQGLYEY
KTVRSLPYLN ACIKESLRMS SPVPGILPRL VPAEGMTWRG HYLPPGTSVS SSIYSVHTDP
NIFPNPEQFI PERWLANENL DHYLVVFGKG SRACIGLNVA WMETYLTFSN FFTSLNMTLF
ETNEQSTDWT DCGNAMIKKH VRVKVDSLAS
//