ID   TYLE_STRFR              Reviewed;         395 AA.
AC   Q9ZHQ4;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 59.
DE   RecName: Full=Demethylmacrocin O-methyltransferase;
DE            EC=2.1.1.102;
DE   AltName: Full=Tylosin biosynthesis protein E;
GN   Name=tylE;
OS   Streptomyces fradiae (Streptomyces roseoflavus).
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=1906;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX   PubMed=10220165; DOI=10.1099/13500872-145-4-855;
RA   Fouces R., Mellado E., Diez B., Barredo J.L.;
RT   "The tylosin biosynthetic cluster from Streptomyces fradiae: genetic
RT   organization of the left region.";
RL   Microbiology 145:855-868(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=T59235;
RX   PubMed=10510490; DOI=10.1038/sj.jim.2900707;
RA   Bate N., Cundliffe E.;
RT   "The mycinose-biosynthetic genes of Streptomyces fradiae, producer of
RT   tylosin.";
RL   J. Ind. Microbiol. Biotechnol. 23:118-122(1999).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=7305323; DOI=10.1128/aac.20.3.370;
RA   Seno E.T., Baltz R.H.;
RT   "Properties of S-adenosyl-L-methionine:macrocin O-methyltransferase in
RT   extracts of Streptomyces fradiae strains which produce normal or elevated
RT   levels of tylosin and in mutants blocked in specific O-methylations.";
RL   Antimicrob. Agents Chemother. 20:370-377(1981).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=3170602; DOI=10.1016/s0021-9258(19)37634-3;
RA   Kreuzman A.J., Turner J.R., Yeh W.K.;
RT   "Two distinctive O-methyltransferases catalyzing penultimate and terminal
RT   reactions of macrolide antibiotic (tylosin) biosynthesis. Substrate
RT   specificity, enzyme inhibition, and kinetic mechanism.";
RL   J. Biol. Chem. 263:15626-15633(1988).
CC   -!- FUNCTION: O-methyltransferase that catalyzes the conversion of
CC       demethylmacrocin to macrocin, the penultimate step of tylosin
CC       antibiotic biosynthesis. Also able to mediate the conversion of
CC       demethyllactenocin to lactenocin. {ECO:0000269|PubMed:10220165,
CC       ECO:0000269|PubMed:10510490, ECO:0000269|PubMed:3170602}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=demethylmacrocin + S-adenosyl-L-methionine = H(+) + macrocin +
CC         S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:17573, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:76819,
CC         ChEBI:CHEBI:76820; EC=2.1.1.102;
CC         Evidence={ECO:0000269|PubMed:3170602};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=6 uM for demethylmacrocin {ECO:0000269|PubMed:3170602};
CC         KM=10 uM for demethyllactenocin {ECO:0000269|PubMed:3170602};
CC         KM=6 uM for AdoMet {ECO:0000269|PubMed:3170602};
CC         Vmax=0.15 umol/min/mg enzyme with demethylmacrocin as substrate
CC         {ECO:0000269|PubMed:3170602};
CC         Vmax=0.14 umol/min/mg enzyme with demethyllactenocin as substrate
CC         {ECO:0000269|PubMed:3170602};
CC       pH dependence:
CC         Optimum pH is 7.8-8.5. {ECO:0000269|PubMed:3170602};
CC   -!- PATHWAY: Antibiotic biosynthesis; tylosin biosynthesis.
CC       {ECO:0000269|PubMed:10510490}.
CC   -!- DISRUPTION PHENOTYPE: No production of demethylmacrocin.
CC       {ECO:0000269|PubMed:7305323}.
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DR   EMBL; AF055922; AAD12164.1; -; Genomic_DNA.
DR   EMBL; AF147703; AAD41815.1; -; Genomic_DNA.
DR   RefSeq; WP_043470778.1; NZ_MCNU01000172.1.
DR   AlphaFoldDB; Q9ZHQ4; -.
DR   SMR; Q9ZHQ4; -.
DR   STRING; 1906.SFRA_26470; -.
DR   KEGG; ag:AAD12164; -.
DR   eggNOG; COG3510; Bacteria.
DR   OMA; MAVQKEA; -.
DR   BioCyc; MetaCyc:MON-18392; -.
DR   UniPathway; UPA01018; -.
DR   GO; GO:0030770; F:demethylmacrocin O-methyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR040800; MycE_N.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   Pfam; PF17843; MycE_N; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Methyltransferase; S-adenosyl-L-methionine;
KW   Transferase.
FT   CHAIN           1..395
FT                   /note="Demethylmacrocin O-methyltransferase"
FT                   /id="PRO_0000418459"
SQ   SEQUENCE   395 AA;  43233 MW;  1BDF12A03EB40C3D CRC64;
     MAVQKEATLV RQIIRAAGGH AADVRELVAE HGPEAVTAVL VDEIVSRAPH PVNDVPVLVE
     LAVRSGDALV PRRLAVAQGA PVRRAAPDDD GFVAMRVEYE LDELVRELFG PCRERAAGTR
     GTTLFPYATS GTGHIDTYFL AAQQATATVL AGCTSAKPDL NELTSRYLTP KWGSLHWFTP
     HYDRHFREYR NEEVRVLEIG IGGYQHPEWG GGSLRMWKHF FHRGLIYGLD IEDKSHAEEQ
     RITTVVGDQN DPGCLTELAA RYGPFDIVID DGSHINEHVR TSFHALFPHV RPGGLYVIED
     LWTAYWPGFG GDSDPGKSDL TSLGLVKSLV DSLQHQELPE DSGRSPGYAD RHVVGLHVYH
     NLAFIEKGVN SEGGIPGWIP RDFDALVAAS SGGAA