ID   SIBG_STRSJ              Reviewed;         351 AA.
AC   C0LTM1;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 1.
DT   03-AUG-2022, entry version 32.
DE   RecName: Full=3-hydroxy-4-methyl-anthranilyl-[aryl-carrier protein] 5-monooxygenase {ECO:0000305};
DE            EC=1.14.13.223 {ECO:0000269|PubMed:21612226};
DE   AltName: Full=FAD/NADH-dependent hydroxylase SibG {ECO:0000303|PubMed:21612226};
GN   Name=sibG {ECO:0000303|PubMed:19270142};
OS   Streptosporangium sibiricum.
OC   Bacteria; Actinobacteria; Streptosporangiales; Streptosporangiaceae;
OC   Streptosporangium.
OX   NCBI_TaxID=457432;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=ATCC 29053 / DSM 44093;
RX   PubMed=19270142; DOI=10.1128/aem.02326-08;
RA   Li W., Khullar A., Chou S., Sacramo A., Gerratana B.;
RT   "Biosynthesis of sibiromycin, a potent antitumor antibiotic.";
RL   Appl. Environ. Microbiol. 75:2869-2878(2009).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   PATHWAY.
RC   STRAIN=ATCC 29053 / DSM 44093;
RX   PubMed=21612226; DOI=10.1021/bi2006114;
RA   Giessen T.W., Kraas F.I., Marahiel M.A.;
RT   "A four-enzyme pathway for 3,5-dihydroxy-4-methylanthranilic acid formation
RT   and incorporation into the antitumor antibiotic sibiromycin.";
RL   Biochemistry 50:5680-5692(2011).
CC   -!- FUNCTION: Involved in the biosynthesis of the antitumor antibiotic
CC       sibiromycin (PubMed:19270142, PubMed:21612226). Hydroxylates the C5
CC       position of the peptidyl carrier protein (PCP)-bound 4-methyl-3-
CC       hydroxyanthranilic acid (4-MHA or 3H4MAA), leading to the formation of
CC       the fully substituted anthranilate moiety found in sibiromycin
CC       (PubMed:21612226). {ECO:0000269|PubMed:19270142,
CC       ECO:0000269|PubMed:21612226}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-hydroxy-4-methylanthranilyl-[aryl-carrier protein] + H(+) +
CC         NADH + O2 = 3,5-dihydroxy-4-methylanthranilyl-[aryl-carrier protein]
CC         + H2O + NAD(+); Xref=Rhea:RHEA:49716, Rhea:RHEA-COMP:12474,
CC         Rhea:RHEA-COMP:12475, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:131912, ChEBI:CHEBI:131913; EC=1.14.13.223;
CC         Evidence={ECO:0000269|PubMed:21612226};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000269|PubMed:21612226};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=743 uM for SibE-PCP-3H4MAA {ECO:0000269|PubMed:21612226};
CC         Note=kcat is 88 min(-1) with SibE-PCP-3H4MAA as substrate.
CC         {ECO:0000269|PubMed:21612226};
CC   -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:19270142,
CC       ECO:0000269|PubMed:21612226}.
CC   -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family.
CC       {ECO:0000305}.
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DR   EMBL; FJ768674; ACN39730.1; -; Genomic_DNA.
DR   SMR; C0LTM1; -.
DR   KEGG; ag:ACN39730; -.
DR   BioCyc; MetaCyc:MON-19739; -.
DR   BRENDA; 1.14.13.223; 14625.
DR   GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR   GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; FAD; Flavoprotein; Monooxygenase; NAD;
KW   Oxidoreductase.
FT   CHAIN           1..351
FT                   /note="3-hydroxy-4-methyl-anthranilyl-[aryl-carrier
FT                   protein] 5-monooxygenase"
FT                   /id="PRO_0000453573"
SQ   SEQUENCE   351 AA;  38088 MW;  F6182159CA42ADC2 CRC64;
     MRILVNGGGP AGMAFAMFAA RSGRGDEITV RDWTGPGDTY GFGVILPPAA VEVFRDAEPD
     LADELNSHIT AWDRLSVHRH GRTASIPAPR LGAMDRRTLL KVLRRRCAER GVRFEHGAVD
     PALGDHDLVV AADGARSVTR RHRAAAFGTT TREIGPAYIW LGADRALEHL RFLVAETPDG
     PAVAHAYPYS PDRSTFLVEA DGAPPPAVLA EWFAGPLGGA RLLENRSRWS RFQEIHNRTW
     SAGNVVLIGD AAHTAHYSIG SGTRLALDDA RALADALCAQ PRLADALKGY EDARRPIVEH
     TQRIGRLSAT WFTRLPDVPM ERLLDDLATR GGQISWRDLA TEGSGAVPVR G