FC1_PHOAM
ID FC1_PHOAM Reviewed; 719 AA.
AC A2PZA5;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Fusicoccadiene synthase {ECO:0000303|PubMed:17360612};
DE Short=FS {ECO:0000303|PubMed:17360612};
DE AltName: Full=Fusicoccin A biosynthetic gene clusters protein 1 {ECO:0000303|PubMed:26734760};
DE AltName: Full=PaDC4:GGS {ECO:0000303|PubMed:17360612};
DE Includes:
DE RecName: Full=Fusicocca-2,10(14)-diene synthase {ECO:0000303|PubMed:17360612};
DE EC=4.2.3.43 {ECO:0000269|PubMed:17360612, ECO:0000269|PubMed:26734760};
DE AltName: Full=Diterpene cyclase 4 {ECO:0000303|PubMed:17360612};
DE Short=DC 4 {ECO:0000303|PubMed:17360612};
DE Includes:
DE RecName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:17360612};
DE Short=GGDP synthase {ECO:0000303|PubMed:17360612};
DE Short=GGS {ECO:0000303|PubMed:17360612};
DE EC=2.5.1.29 {ECO:0000269|PubMed:17360612, ECO:0000269|PubMed:26734760};
GN Name=PaFS {ECO:0000303|PubMed:17360612};
GN Synonyms=orf1 {ECO:0000303|PubMed:22870285};
OS Phomopsis amygdali (Fusicoccum amygdali).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Diaporthales; Diaporthaceae; Diaporthe.
OX NCBI_TaxID=1214568;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF ASP-92 AND ASP-474, AND PATHWAY.
RC STRAIN=N2;
RX PubMed=17360612; DOI=10.1073/pnas.0608426104;
RA Toyomasu T., Tsukahara M., Kaneko A., Niida R., Mitsuhashi W., Dairi T.,
RA Kato N., Sassa T.;
RT "Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in
RT fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3084-3088(2007).
RN [2]
RP FUNCTION.
RX PubMed=21299202; DOI=10.1021/ja107785u;
RA Ono Y., Minami A., Noike M., Higuchi Y., Toyomasu T., Sassa T., Kato N.,
RA Dairi T.;
RT "Dioxygenases, key enzymes to determine the aglycon structures of
RT fusicoccin and brassicicene, diterpene compounds produced by fungi.";
RL J. Am. Chem. Soc. 133:2548-2555(2011).
RN [3]
RP FUNCTION.
RX PubMed=22287087; DOI=10.1002/cbic.201100725;
RA Noike M., Liu C., Ono Y., Hamano Y., Toyomasu T., Sassa T., Kato N.,
RA Dairi T.;
RT "An enzyme catalyzing O-prenylation of the glucose moiety of fusicoccin A,
RT a diterpene glucoside produced by the fungus Phomopsis amygdali.";
RL ChemBioChem 13:566-573(2012).
RN [4]
RP FUNCTION.
RX PubMed=22870285; DOI=10.1371/journal.pone.0042090;
RA Noike M., Ono Y., Araki Y., Tanio R., Higuchi Y., Nitta H., Hamano Y.,
RA Toyomasu T., Sassa T., Kato N., Dairi T.;
RT "Molecular breeding of a fungus producing a precursor diterpene suitable
RT for semi-synthesis by dissection of the biosynthetic machinery.";
RL PLoS ONE 7:E42090-E42090(2012).
RN [5] {ECO:0007744|PDB:5ER8, ECO:0007744|PDB:5ERM, ECO:0007744|PDB:5ERN, ECO:0007744|PDB:5ERO}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-344 AND 389-719 IN COMPLEX WITH
RP SUBSTRATE, SUBUNIT, MUTAGENESIS OF ASP-92 AND ASP-474, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=26734760; DOI=10.1021/acschembio.5b00960;
RA Chen M., Chou W.K., Toyomasu T., Cane D.E., Christianson D.W.;
RT "Structure and function of fusicoccadiene synthase, a hexameric
RT bifunctional diterpene synthase.";
RL ACS Chem. Biol. 11:889-899(2016).
CC -!- FUNCTION: Multifunctional diterpene synthase; part of the 2 gene
CC clusters that mediate the biosynthesis of fusicoccins, diterpene
CC glucosides that display phytohormone-like activity and function as
CC potent activators of plasma membrane H(+)-ATPases in plants by
CC modifying 14-3-3 proteins and cause the plant disease constriction
CC canker (PubMed:17360612, PubMed:26734760). The first step in the
CC pathway is performed by the fusicoccadiene synthase PaFS that possesses
CC both prenyl transferase and terpene cyclase activity, converting
CC isopentenyl diphosphate and dimethylallyl diphosphate into
CC geranylgeranyl diphosphate (GGDP) and successively converting GGDP into
CC fusicocca-2,10(14)-diene, a precursor for fusicoccin H
CC (PubMed:17360612, PubMed:26734760). Fusicoccadiene synthase is an
CC allosteric enzyme for GGPP cyclization that generates 64%
CC fusicoccadiene, 9% delta-araneosene, and one additional unidentified
CC diterpene product, when incubated with GGPP (PubMed:26734760). In the
CC absence of isopentenyl diphosphate (IPP), PaFS can also solvolyze the
CC shorter chain geranyl diphosphate (GPP) and farnesyl diphosphate (FPP)
CC as alternative substrates to yield predominantly acyclic products. FPP
CC is converted to farnesol (60.5%), nerolidol (14.0%), and farnesene
CC (14.0%), while GPP is converted to a mixture of geraniol (59.5%) and
CC linalool (35.0%) (PubMed:26734760). The second step is the oxidation at
CC the C-8 position by the cytochrome P450 monooxygenase PaP450-2 to yield
CC fusicocca-2,10(14)-diene-8-beta-ol (PubMed:22870285). The cytochrome
CC P450 monooxygenase PaP450-1 then catalyzes the hydroxylation at the C-
CC 16 position to produce fusicocca-2,10(14)-diene-8-beta,16-diol
CC (PubMed:22870285). The dioxygenase fc-dox then catalyzes the 16-
CC oxydation of fusicocca-2,10(14)-diene-8-beta,16-diol to yield an
CC aldehyde (8-beta-hydroxyfusicocca-1,10(14)-dien-16-al)
CC (PubMed:21299202, PubMed:22870285). The short-chain
CC dehydrogenase/reductase fc-sdr catalyzes the reduction of the aldehyde
CC to yield fusicocca-1,10(14)-diene-8-beta,16-diol (PubMed:21299202,
CC PubMed:22870285). The next step is the hydroxylation at C-9 performed
CC by the cytochrome P450 monooxygenase PaP450-3 that leads to fusicoccin
CC H aglycon which is glycosylated to fusicoccin H by the O-
CC glycosyltransferase PAGT (PubMed:22870285). Hydroxylation at C-12 by
CC the cytochrome P450 monooxygenase PaP450-4 leads then to the production
CC of fusicoccin Q and is followed by methylation by the O-
CC methyltransferase PAMT to yield fusicoccin P (PubMed:22870285).
CC Fusicoccin P is further converted to fusicoccin J via prenylation by
CC the O-glucose prenyltransferase PaPT (PubMed:22287087). Cytochrome P450
CC monooxygenase PaP450-5 then performs hydroxylation at C-19 to yield
CC dideacetyl-fusicoccin A which is acetylated to 3'-O-deacetyl-fusicoccin
CC A by the O-acetyltransferase PaAT-2 (PubMed:22870285). Finally, a
CC another acetylation by the O-acetyltransferase PaAT-1 yields fusicoccin
CC A (PubMed:22870285). {ECO:0000269|PubMed:17360612,
CC ECO:0000269|PubMed:21299202, ECO:0000269|PubMed:22287087,
CC ECO:0000269|PubMed:22870285, ECO:0000269|PubMed:26734760}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=geranylgeranyl diphosphate = diphosphate + fusicocca-2,10(14)-
CC diene; Xref=Rhea:RHEA:26245, ChEBI:CHEBI:33019, ChEBI:CHEBI:52463,
CC ChEBI:CHEBI:57533; EC=4.2.3.43;
CC Evidence={ECO:0000269|PubMed:17360612, ECO:0000269|PubMed:26734760};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate =
CC (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate;
CC Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29;
CC Evidence={ECO:0000269|PubMed:17360612, ECO:0000269|PubMed:26734760};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.2 uM for GPP {ECO:0000269|PubMed:26734760};
CC KM=0.14 uM for FPP {ECO:0000269|PubMed:26734760};
CC KM=0.632 uM for GGPP {ECO:0000269|PubMed:26734760};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:17360612,
CC ECO:0000269|PubMed:26734760}.
CC -!- SUBUNIT: Hexamer. {ECO:0000269|PubMed:26734760}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the terpene synthase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the FPP/GGPP synthase
CC family. {ECO:0000305}.
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DR EMBL; AB267396; BAF45924.1; -; mRNA.
DR EMBL; AB272062; BAF45925.1; -; Genomic_DNA.
DR PDB; 5ER8; X-ray; 2.50 A; A/B=1-344.
DR PDB; 5ERM; X-ray; 2.30 A; A/B=1-344.
DR PDB; 5ERN; X-ray; 2.43 A; A/B=389-719.
DR PDB; 5ERO; X-ray; 2.55 A; A/B/C=389-719.
DR PDB; 7JTH; EM; 4.00 A; A/B/C/D/E/F/G/H=1-719.
DR PDBsum; 5ER8; -.
DR PDBsum; 5ERM; -.
DR PDBsum; 5ERN; -.
DR PDBsum; 5ERO; -.
DR PDBsum; 7JTH; -.
DR AlphaFoldDB; A2PZA5; -.
DR SMR; A2PZA5; -.
DR KEGG; ag:BAF45924; -.
DR BioCyc; MetaCyc:MON-14878; -.
DR BRENDA; 4.2.3.43; 10693.
DR GO; GO:0004311; F:farnesyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.600.10; -; 2.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 2.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Transferase.
FT CHAIN 1..719
FT /note="Fusicoccadiene synthase"
FT /id="PRO_0000418511"
FT REGION 1..334
FT /note="Fusicocca-2,10(14)-diene synthase"
FT /evidence="ECO:0000305|PubMed:17360612"
FT REGION 335..719
FT /note="Geranylgeranyl diphosphate synthase"
FT /evidence="ECO:0000305|PubMed:17360612"
FT REGION 358..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26734760,
FT ECO:0007744|PDB:5ER8"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 96
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26734760,
FT ECO:0007744|PDB:5ER8"
FT BINDING 188..191
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26734760,
FT ECO:0007744|PDB:5ER8"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26734760,
FT ECO:0007744|PDB:5ER8"
FT BINDING 236..240
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26734760,
FT ECO:0007744|PDB:5ER8"
FT BINDING 325..326
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26734760,
FT ECO:0007744|PDB:5ER8"
FT BINDING 435
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 438
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 467
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 478
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 478
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 483
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 484
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 561
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 562
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 602
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 609
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 619
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 629
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT MUTAGEN 92
FT /note="D->A: Abolishes the binding of catalytically
FT essential Mg(2+) ions and inactivates cyclase activity."
FT /evidence="ECO:0000269|PubMed:17360612,
FT ECO:0000269|PubMed:26734760"
FT MUTAGEN 474
FT /note="D->A: Abolishes prenyl transferase activity."
FT /evidence="ECO:0000269|PubMed:17360612,
FT ECO:0000269|PubMed:26734760"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:5ER8"
FT TURN 17..22
FT /evidence="ECO:0007829|PDB:5ER8"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 31..48
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 65..69
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 78..95
FT /evidence="ECO:0007829|PDB:5ERM"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:5ER8"
FT HELIX 141..148
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 152..161
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 163..167
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 194..205
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:5ERM"
FT TURN 218..220
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 222..235
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 237..247
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 255..262
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 267..291
FT /evidence="ECO:0007829|PDB:5ERM"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:5ERM"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 300..308
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 310..320
FT /evidence="ECO:0007829|PDB:5ERM"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 334..341
FT /evidence="ECO:0007829|PDB:5ERM"
FT HELIX 415..422
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 424..429
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 437..449
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 453..474
FT /evidence="ECO:0007829|PDB:5ERN"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:5ERN"
FT STRAND 482..485
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 490..513
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 522..544
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 551..559
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 562..575
FT /evidence="ECO:0007829|PDB:5ERN"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:5ERO"
FT HELIX 583..607
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 613..619
FT /evidence="ECO:0007829|PDB:5ERO"
FT HELIX 623..627
FT /evidence="ECO:0007829|PDB:5ERO"
FT HELIX 632..640
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 645..656
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 662..674
FT /evidence="ECO:0007829|PDB:5ERN"
FT HELIX 678..702
FT /evidence="ECO:0007829|PDB:5ERN"
FT STRAND 703..705
FT /evidence="ECO:0007829|PDB:5ERO"
FT HELIX 708..715
FT /evidence="ECO:0007829|PDB:5ERN"
SQ SEQUENCE 719 AA; 81614 MW; 68BD577F8E254DAE CRC64;
MEFKYSEVVE PSTYYTEGLC EGIDVRKSKF TTLEDRGAIR AHEDWNKHIG PCGEYRGTLG
PRFSFISVAV PECIPERLEV ISYANEFAFL HDDVTDHVGH DTGEVENDEM MTVFLEAAHT
GAIDTSNKVD IRRAGKKRIQ SQLFLEMLAI DPECAKTTMK SWARFVEVGS SRQHETRFVE
LAKYIPYRIM DVGEMFWFGL VTFGLGLHIP DHELELCREL MANAWIAVGL QNDIWSWPKE
RDAATLHGKD HVVNAIWVLM QEHQTDVDGA MQICRKLIVE YVAKYLEVIE ATKNDESISL
DLRKYLDAML YSISGNVVWS LECPRYNPDV SFNKTQLEWM RQGLPSLESC PVLARSPEID
SDESAVSPTA DESDSTEDSL GSGSRQDSSL STGLSLSPVH SNEGKDLQRV DTDHIFFEKA
VLEAPYDYIA SMPSKGVRDQ FIDALNDWLR VPDVKVGKIK DAVRVLHNSS LLLDDFQDNS
PLRRGKPSTH NIFGSAQTVN TATYSIIKAI GQIMEFSAGE SVQEVMNSIM ILFQGQAMDL
FWTYNGHVPS EEEYYRMIDQ KTGQLFSIAT SLLLNAADNE IPRTKIQSCL HRLTRLLGRC
FQIRDDYQNL VSADYTKQKG FCEDLDEGKW SLALIHMIHK QRSHMALLNV LSTGRKHGGM
TLEQKQFVLD IIEEEKSLDY TRSVMMDLHV QLRAEIGRIE ILLDSPNPAM RLLLELLRV
