EIZFM_STRCO
ID EIZFM_STRCO Reviewed; 461 AA.
AC Q9K498;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Bifunctional albaflavenone monooxygenase/terpene synthase {ECO:0000305};
DE AltName: Full=Cytochrome P450 170A1 {ECO:0000303|PubMed:18234666};
DE Short=CYP170A1 {ECO:0000303|PubMed:18234666};
DE Includes:
DE RecName: Full=Epi-isozizaene 5-monooxygenase {ECO:0000305};
DE EC=1.14.15.39 {ECO:0000269|PubMed:18234666, ECO:0000269|PubMed:19858213};
DE Includes:
DE RecName: Full=Beta-farnesene synthase {ECO:0000305};
DE EC=4.2.3.47 {ECO:0000269|PubMed:19858213};
GN OrderedLocusNames=SCO5223;
OS Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces; Streptomyces albidoflavus group.
OX NCBI_TaxID=100226;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=12000953; DOI=10.1038/417141a;
RA Bentley S.D., Chater K.F., Cerdeno-Tarraga A.-M., Challis G.L.,
RA Thomson N.R., James K.D., Harris D.E., Quail M.A., Kieser H., Harper D.,
RA Bateman A., Brown S., Chandra G., Chen C.W., Collins M., Cronin A.,
RA Fraser A., Goble A., Hidalgo J., Hornsby T., Howarth S., Huang C.-H.,
RA Kieser T., Larke L., Murphy L.D., Oliver K., O'Neil S., Rabbinowitsch E.,
RA Rajandream M.A., Rutherford K.M., Rutter S., Seeger K., Saunders D.,
RA Sharp S., Squares R., Squares S., Taylor K., Warren T., Wietzorrek A.,
RA Woodward J.R., Barrell B.G., Parkhill J., Hopwood D.A.;
RT "Complete genome sequence of the model actinomycete Streptomyces coelicolor
RT A3(2).";
RL Nature 417:141-147(2002).
RN [2]
RP FUNCTION AS AN EPIISOZIZAENE MONOOXYGENASE AND IN THE ALBAFLAVENONE
RP BIOSYNTHESIS, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18234666; DOI=10.1074/jbc.m710421200;
RA Zhao B., Lin X., Lei L., Lamb D.C., Kelly S.L., Waterman M.R., Cane D.E.;
RT "Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces
RT coelicolor A3(2).";
RL J. Biol. Chem. 283:8183-8189(2008).
RN [3] {ECO:0007744|PDB:3DBG, ECO:0007744|PDB:3EL3}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH HEME AND SUBSTRATE,
RP FUNCTION AS AN EPIISOZIZAENE MONOOXYGENASE AND AS BETA-FARNESENE SYNTHASE,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT, AND
RP MUTAGENESIS OF 253-ASP--ASP-257.
RX PubMed=19858213; DOI=10.1074/jbc.m109.064683;
RA Zhao B., Lei L., Vassylyev D.G., Lin X., Cane D.E., Kelly S.L., Yuan H.,
RA Lamb D.C., Waterman M.R.;
RT "Crystal structure of albaflavenone monooxygenase containing a moonlighting
RT terpene synthase active site.";
RL J. Biol. Chem. 284:36711-36719(2009).
CC -!- FUNCTION: Involved in the biosynthesis of the sesquiterpenoid
CC antibiotic albaflavenone. Catalyzes the two-step allylic oxidation of
CC epi-isozizaene to albaflavenone. First carries out a non-stereo-
CC specific oxidation of epi-isozizaene to give a mixture of the
CC albaflavenol epimers ((5R)-albaflavenol and (5S)-albaflavenol), each of
CC which can serve as substrate for the second oxidation to yield
CC albaflavenone. This is quite different from most other P450s which
CC catalyze regio- and stereospecific oxidation (PubMed:18234666,
CC PubMed:19858213). In addition, displays a farnesene synthase activity
CC with farnesyl diphosphate (FPP) as substrate (PubMed:19858213).
CC {ECO:0000269|PubMed:18234666, ECO:0000269|PubMed:19858213}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-epi-isozizaene + 4 H(+) + 2 O2 + 4 reduced [2Fe-2S]-
CC [ferredoxin] = albaflavenone + 3 H2O + 4 oxidized [2Fe-2S]-
CC [ferredoxin]; Xref=Rhea:RHEA:32439, Rhea:RHEA-COMP:10000, Rhea:RHEA-
CC COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:51458,
CC ChEBI:CHEBI:51460; EC=1.14.15.39;
CC Evidence={ECO:0000269|PubMed:18234666, ECO:0000269|PubMed:19858213};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32440;
CC Evidence={ECO:0000269|PubMed:18234666, ECO:0000269|PubMed:19858213};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate = (E)-beta-farnesene +
CC diphosphate; Xref=Rhea:RHEA:27425, ChEBI:CHEBI:10418,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:175763; EC=4.2.3.47;
CC Evidence={ECO:0000269|PubMed:19858213};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-epi-isozizaene + 2 H(+) + O2 + 2 reduced [2Fe-2S]-
CC [ferredoxin] = (5R)-albaflavenol + H2O + 2 oxidized [2Fe-2S]-
CC [ferredoxin]; Xref=Rhea:RHEA:25984, Rhea:RHEA-COMP:10000, Rhea:RHEA-
CC COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:51458,
CC ChEBI:CHEBI:51479; Evidence={ECO:0000269|PubMed:18234666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25985;
CC Evidence={ECO:0000269|PubMed:18234666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-epi-isozizaene + 2 H(+) + O2 + 2 reduced [2Fe-2S]-
CC [ferredoxin] = (5S)-albaflavenol + H2O + 2 oxidized [2Fe-2S]-
CC [ferredoxin]; Xref=Rhea:RHEA:25976, Rhea:RHEA-COMP:10000, Rhea:RHEA-
CC COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:51458,
CC ChEBI:CHEBI:51480; Evidence={ECO:0000269|PubMed:18234666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25977;
CC Evidence={ECO:0000269|PubMed:18234666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-albaflavenol + 2 H(+) + O2 + 2 reduced [2Fe-2S]-
CC [ferredoxin] = albaflavenone + 2 H2O + 2 oxidized [2Fe-2S]-
CC [ferredoxin]; Xref=Rhea:RHEA:25988, Rhea:RHEA-COMP:10000, Rhea:RHEA-
CC COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:51460,
CC ChEBI:CHEBI:51479; Evidence={ECO:0000269|PubMed:18234666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25989;
CC Evidence={ECO:0000269|PubMed:18234666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-albaflavenol + 2 H(+) + O2 + 2 reduced [2Fe-2S]-
CC [ferredoxin] = albaflavenone + 2 H2O + 2 oxidized [2Fe-2S]-
CC [ferredoxin]; Xref=Rhea:RHEA:25980, Rhea:RHEA-COMP:10000, Rhea:RHEA-
CC COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:51460,
CC ChEBI:CHEBI:51480; Evidence={ECO:0000269|PubMed:18234666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25981;
CC Evidence={ECO:0000269|PubMed:18234666};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19858213};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:19858213};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:19858213};
CC Note=Divalent metal cations. Mg(2+), Ca(2+) or Mn(2+) ions for
CC farnesene synthase activity. {ECO:0000269|PubMed:19858213};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:19858213};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.8 uM for FPP (in the presence of magnesium ions at 30 degrees
CC Celsius and at pH 5.5) {ECO:0000269|PubMed:19858213};
CC Note=kcat is 0.019 sec(-1) with farnesyl diphosphate (FPP) as
CC substrate (in the presence of magnesium ions at 30 degrees Celsius
CC and at pH 5.5).;
CC pH dependence:
CC Optimum pH is between 7 and 8.2 for monooxygenase activity and
CC between 5.5 and 6.5 for farnesene synthase activity.
CC {ECO:0000269|PubMed:19858213};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19858213}.
CC -!- DISRUPTION PHENOTYPE: Disruption abolishes biosynthesis of both
CC albaflavenone and the albaflavenols, but not epi-isozizaene.
CC {ECO:0000269|PubMed:18234666}.
CC -!- MISCELLANEOUS: Both enzymatic and structural data demonstrate that
CC CYP170A1 is a rare bifunctional enzyme having two distinct active sites
CC within a traditional P450 polypeptide chain that individually catalyze
CC two apparently unrelated biochemical reactions.
CC {ECO:0000269|PubMed:19858213}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AL939123; CAB94608.1; -; Genomic_DNA.
DR RefSeq; NP_629370.1; NC_003888.3.
DR RefSeq; WP_011030120.1; NZ_VNID01000008.1.
DR PDB; 3DBG; X-ray; 2.60 A; A/B=1-461.
DR PDB; 3EL3; X-ray; 3.30 A; A/B=1-461.
DR PDBsum; 3DBG; -.
DR PDBsum; 3EL3; -.
DR AlphaFoldDB; Q9K498; -.
DR SMR; Q9K498; -.
DR STRING; 100226.SCO5223; -.
DR MoonProt; Q9K498; -.
DR GeneID; 1100664; -.
DR KEGG; sco:SCO5223; -.
DR PATRIC; fig|100226.15.peg.5307; -.
DR eggNOG; COG2124; Bacteria.
DR HOGENOM; CLU_001570_5_1_11; -.
DR InParanoid; Q9K498; -.
DR OMA; IQPAFRL; -.
DR PhylomeDB; Q9K498; -.
DR BioCyc; MetaCyc:MON-13905; -.
DR BRENDA; 4.2.3.37; 5998.
DR EvolutionaryTrace; Q9K498; -.
DR Proteomes; UP000001973; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
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; IDA:UniProtKB.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0010334; F:sesquiterpene synthase activity; IMP:CAFA.
DR GO; GO:0010333; F:terpene synthase activity; IDA:UniProtKB.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IMP:CAFA.
DR GO; GO:0042181; P:ketone biosynthetic process; IMP:CAFA.
DR GO; GO:0051762; P:sesquiterpene biosynthetic process; IMP:CAFA.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Lyase; Magnesium; Metal-binding; Monooxygenase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..461
FT /note="Bifunctional albaflavenone monooxygenase/terpene
FT synthase"
FT /id="PRO_0000418620"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 410
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:0000269|PubMed:19858213"
FT MUTAGEN 253..257
FT /note="DDNGD->AANGA: Loss of farnesene synthase activity,
FT whereas the P450 monooxygenase activity is retained."
FT /evidence="ECO:0000269|PubMed:19858213"
FT HELIX 35..42
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 44..51
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 73..81
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:3EL3"
FT TURN 89..92
FT /evidence="ECO:0007829|PDB:3EL3"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:3EL3"
FT TURN 97..101
FT /evidence="ECO:0007829|PDB:3EL3"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:3EL3"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:3DBG"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:3DBG"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 132..145
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 154..170
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 177..192
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 220..234
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 244..248
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 261..292
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 294..308
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 315..318
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 322..334
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 341..344
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 366..370
FT /evidence="ECO:0007829|PDB:3DBG"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:3DBG"
FT TURN 377..380
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 384..387
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 389..392
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 405..409
FT /evidence="ECO:0007829|PDB:3DBG"
FT HELIX 413..430
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 431..435
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 440..453
FT /evidence="ECO:0007829|PDB:3DBG"
FT STRAND 455..460
FT /evidence="ECO:0007829|PDB:3DBG"
SQ SEQUENCE 461 AA; 50938 MW; 10282E36A405B57E CRC64;
MTVESVNPET RAPAAPGAPE LREPPVAGGG VPLLGHGWRL ARDPLAFMSQ LRDHGDVVRI
KLGPKTVYAV TNPELTGALA LNPDYHIAGP LWESLEGLLG KEGVATANGP LHRRQRRTIQ
PAFRLDAIPA YGPIMEEEAH ALTERWQPGK TVDATSESFR VAVRVAARCL LRGQYMDERA
ERLCVALATV FRGMYRRMVV PLGPLYRLPL PANRRFNDAL ADLHLLVDEI IAERRASGQK
PDDLLTALLE AKDDNGDPIG EQEIHDQVVA ILTPGSETIA STIMWLLQAL ADHPEHADRI
RDEVEAVTGG RPVAFEDVRK LRHTGNVIVE AMRLRPAVWV LTRRAVAESE LGGYRIPAGA
DIIYSPYAIQ RDPKSYDDNL EFDPDRWLPE RAANVPKYAM KPFSAGKRKC PSDHFSMAQL
TLITAALATK YRFEQVAGSN DAVRVGITLR PHDLLVRPVA R
