PTLH_STRAW
ID PTLH_STRAW Reviewed; 285 AA.
AC Q82IZ1;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=1-deoxypentalenic acid 11-beta-hydroxylase;
DE EC=1.14.11.35;
DE AltName: Full=Neopentalenolactone biosynthesis protein H;
GN Name=ptlH; OrderedLocusNames=SAV_2991;
OS Streptomyces avermitilis (strain ATCC 31267 / DSM 46492 / JCM 5070 / NBRC
OS 14893 / NCIMB 12804 / NRRL 8165 / MA-4680).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=227882;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 / NRRL
RC 8165 / MA-4680;
RX PubMed=11572948; DOI=10.1073/pnas.211433198;
RA Omura S., Ikeda H., Ishikawa J., Hanamoto A., Takahashi C., Shinose M.,
RA Takahashi Y., Horikawa H., Nakazawa H., Osonoe T., Kikuchi H., Shiba T.,
RA Sakaki Y., Hattori M.;
RT "Genome sequence of an industrial microorganism Streptomyces avermitilis:
RT deducing the ability of producing secondary metabolites.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12215-12220(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 / NRRL
RC 8165 / MA-4680;
RX PubMed=12692562; DOI=10.1038/nbt820;
RA Ikeda H., Ishikawa J., Hanamoto A., Shinose M., Kikuchi H., Shiba T.,
RA Sakaki Y., Hattori M., Omura S.;
RT "Complete genome sequence and comparative analysis of the industrial
RT microorganism Streptomyces avermitilis.";
RL Nat. Biotechnol. 21:526-531(2003).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 / NRRL
RC 8165 / MA-4680;
RX PubMed=16704250; DOI=10.1021/ja061469i;
RA You Z., Omura S., Ikeda H., Cane D.E.;
RT "Pentalenolactone biosynthesis. Molecular cloning and assignment of
RT biochemical function to PtlH, a non-heme iron dioxygenase of Streptomyces
RT avermitilis.";
RL J. Am. Chem. Soc. 128:6566-6567(2006).
RN [4]
RP PATHWAY.
RC STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 / NRRL
RC 8165 / MA-4680;
RX PubMed=21250661; DOI=10.1021/bi1019786;
RA Seo M.J., Zhu D., Endo S., Ikeda H., Cane D.E.;
RT "Genome mining in Streptomyces. Elucidation of the role of Baeyer-Villiger
RT monooxygenases and non-heme iron-dependent dehydrogenase/oxygenases in the
RT final steps of the biosynthesis of pentalenolactone and
RT neopentalenolactone.";
RL Biochemistry 50:1739-1754(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.31 ANGSTROMS) IN COMPLEX WITH IRON;
RP ALPHA-KETOGLUTARATE AND ENT-1-DEOXYPENTALENIC ACID, FUNCTION, CATALYTIC
RP ACTIVITY, COFACTOR, AND MUTAGENESIS OF ARG-117 AND ARG-188.
RC STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 / NRRL
RC 8165 / MA-4680;
RX PubMed=17942405; DOI=10.1074/jbc.m706358200;
RA You Z., Omura S., Ikeda H., Cane D.E., Jogl G.;
RT "Crystal structure of the non-heme iron dioxygenase PtlH in
RT pentalenolactone biosynthesis.";
RL J. Biol. Chem. 282:36552-36560(2007).
CC -!- FUNCTION: Catalyzes the conversion of 1-deoxypentalenic acid to 11-
CC beta-hydroxy-1-deoxypentalenic acid in the biosynthesis of
CC neopentalenolactone antibiotic. {ECO:0000269|PubMed:16704250,
CC ECO:0000269|PubMed:17942405}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-deoxypentalenate + 2-oxoglutarate + O2 = 1-deoxy-11beta-
CC hydroxypentalenate + CO2 + succinate; Xref=Rhea:RHEA:34619,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:68650, ChEBI:CHEBI:70779;
CC EC=1.14.11.35; Evidence={ECO:0000269|PubMed:16704250,
CC ECO:0000269|PubMed:17942405};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:17942405};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.57 mM for 1-deoxypentalenic acid {ECO:0000269|PubMed:16704250};
CC Note=kcat is 4.2 sec(-1) with 1-deoxypentalenic acid.;
CC pH dependence:
CC Optimum pH is 6.0. {ECO:0000269|PubMed:16704250};
CC -!- PATHWAY: Antibiotic biosynthesis; neopentalenolactone biosynthesis.
CC {ECO:0000269|PubMed:21250661}.
CC -!- MISCELLANEOUS: S.avermitilis does not produce pentalenolactone itself
CC in vivo but instead a group of new metabolites that are
CC neopentalenolactone derivatives. {ECO:0000305|PubMed:21250661}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; BA000030; BAC70702.2; -; Genomic_DNA.
DR RefSeq; WP_037648981.1; NZ_JZJK01000090.1.
DR PDB; 2RDN; X-ray; 1.35 A; A=1-285.
DR PDB; 2RDQ; X-ray; 1.31 A; A=1-285.
DR PDB; 2RDR; X-ray; 1.70 A; A=1-285.
DR PDB; 2RDS; X-ray; 1.65 A; A=1-285.
DR PDBsum; 2RDN; -.
DR PDBsum; 2RDQ; -.
DR PDBsum; 2RDR; -.
DR PDBsum; 2RDS; -.
DR AlphaFoldDB; Q82IZ1; -.
DR SMR; Q82IZ1; -.
DR STRING; 227882.SAV_2991; -.
DR DrugBank; DB06903; (1S,3aS,5aR,8aS)-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylic acid.
DR EnsemblBacteria; BAC70702; BAC70702; SAVERM_2991.
DR KEGG; sma:SAVERM_2991; -.
DR eggNOG; COG5285; Bacteria.
DR HOGENOM; CLU_948969_0_0_11; -.
DR OMA; STTIRYY; -.
DR OrthoDB; 1070946at2; -.
DR BioCyc; MetaCyc:MON-16835; -.
DR BRENDA; 1.14.11.35; 5980.
DR UniPathway; UPA01021; -.
DR EvolutionaryTrace; Q82IZ1; -.
DR Proteomes; UP000000428; Chromosome.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IDA:UniProtKB.
DR GO; GO:1901336; P:lactone biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Dioxygenase; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome; Vitamin C.
FT CHAIN 1..285
FT /note="1-deoxypentalenic acid 11-beta-hydroxylase"
FT /id="PRO_0000422000"
FT BINDING 117
FT /ligand="substrate"
FT BINDING 137..139
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT BINDING 137
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17942405"
FT BINDING 139
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17942405"
FT BINDING 153
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:17942405"
FT BINDING 188
FT /ligand="substrate"
FT BINDING 226
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17942405"
FT BINDING 228
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:17942405"
FT BINDING 240
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:17942405"
FT MUTAGEN 117
FT /note="R->Q: Abolishes 1-deoxypentalenic acid 11-beta-
FT hydroxylase activity."
FT /evidence="ECO:0000269|PubMed:17942405"
FT MUTAGEN 188
FT /note="R->Q: Strong reduction of 1-deoxypentalenic acid 11-
FT beta-hydroxylase activity."
FT /evidence="ECO:0000269|PubMed:17942405"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 39..56
FT /evidence="ECO:0007829|PDB:2RDQ"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 78..84
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 87..91
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 94..104
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 108..119
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:2RDQ"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:2RDQ"
FT TURN 170..173
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:2RDQ"
FT STRAND 240..249
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:2RDQ"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:2RDN"
SQ SEQUENCE 285 AA; 32264 MW; 9E48B0F63540D4B3 CRC64;
MTNVTGDYTD CTPLLGDRAA LDSFYEEHGY LFLRNVLDRD LVKTVAEQMR EGLVALGAAD
PHATLEELTI DSFESVDEVA MHDYVKYDAF WNNPSTIKVF EQVFGEPVFV FLSTTIRYYP
SQAGSEEPSF HYLTPFHQDG FYIGPNQDFR TFWIPLIRTT RESGGVALAD GSHRRGKRDH
VLNESFRRFG HPVRGIPPTE VSEDEHLLHS PMEPGDILLF HAHMCHKSIP NLSKDPRLMR
MSMDTRVQPA KSHRGFNAMT PWTESAKDAS KGIMAKITGT PTDVE
