TYLF_STRFR
ID TYLF_STRFR Reviewed; 256 AA.
AC Q9S4D5; Q54169; Q79ED6;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Macrocin O-methyltransferase;
DE Short=MacOMeTase;
DE EC=2.1.1.101;
DE AltName: Full=Tylosin biosynthesis protein F;
GN Name=tylF;
OS Streptomyces fradiae (Streptomyces roseoflavus).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1906;
RN [1]
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-38, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=3479787; DOI=10.1073/pnas.84.23.8248;
RA Fishman S.E., Cox K., Larson J.L., Reynolds P.A., Seno E.T., Yeh W.K.,
RA Van Frank R., Hershberger C.L.;
RT "Cloning genes for the biosynthesis of a macrolide antibiotic.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8248-8252(1987).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=3170601; DOI=10.1016/s0021-9258(19)37633-1;
RA Bauer N.J., Kreuzman A.J., Dotzlaf J.E., Yeh W.K.;
RT "Purification, characterization, and kinetic mechanism of S-adenosyl-L-
RT methionine:macrocin O-methyltransferase from Streptomyces fradiae.";
RL J. Biol. Chem. 263:15619-15625(1988).
RN [5]
RP 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 macrocin
CC to tylosin, the ultimate step of tylosin antibiotic biosynthesis. Also
CC able to mediate the conversion of lactenocin to desmycosin.
CC {ECO:0000269|PubMed:10220165, ECO:0000269|PubMed:10510490,
CC ECO:0000269|PubMed:3170601, ECO:0000269|PubMed:3479787}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=macrocin + S-adenosyl-L-methionine = H(+) + S-adenosyl-L-
CC homocysteine + tylosin; Xref=Rhea:RHEA:17269, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:76820,
CC ChEBI:CHEBI:77047; EC=2.1.1.101;
CC Evidence={ECO:0000269|PubMed:3170601, ECO:0000269|PubMed:3479787};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for macrocin {ECO:0000269|PubMed:3170601,
CC ECO:0000269|PubMed:3170602};
CC KM=7 uM for lactenocin {ECO:0000269|PubMed:3170601,
CC ECO:0000269|PubMed:3170602};
CC KM=23 uM for AdoMet {ECO:0000269|PubMed:3170601,
CC ECO:0000269|PubMed:3170602};
CC Vmax=0.23 umol/min/mg enzyme with macrocin as substrate
CC {ECO:0000269|PubMed:3170601, ECO:0000269|PubMed:3170602};
CC Vmax=0.21 umol/min/mg enzyme with lactenocin as substrate
CC {ECO:0000269|PubMed:3170601, ECO:0000269|PubMed:3170602};
CC pH dependence:
CC Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:3170601,
CC ECO:0000269|PubMed:3170602};
CC -!- PATHWAY: Antibiotic biosynthesis; tylosin biosynthesis.
CC {ECO:0000269|PubMed:10510490}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:3170601}.
CC -!- SIMILARITY: Belongs to the methyltransferase TylF/MycF family.
CC {ECO:0000305}.
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DR EMBL; AF147703; AAD41819.1; -; Genomic_DNA.
DR EMBL; AF055922; AAD12168.1; -; Genomic_DNA.
DR EMBL; J03008; AAA26835.1; -; Genomic_DNA.
DR PIR; A39965; A39965.
DR AlphaFoldDB; Q9S4D5; -.
DR SMR; Q9S4D5; -.
DR STRING; 1906.SFRA_26450; -.
DR KEGG; ag:AAD41819; -.
DR eggNOG; COG4122; Bacteria.
DR OMA; WRGGACI; -.
DR BioCyc; MetaCyc:MON-18393; -.
DR BRENDA; 2.1.1.101; 5932.
DR UniPathway; UPA01018; -.
DR GO; GO:0030769; F:macrocin O-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR008884; TylF_MeTrfase.
DR PANTHER; PTHR40036; PTHR40036; 1.
DR Pfam; PF05711; TylF; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; Magnesium; Metal-binding; Methyltransferase;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..256
FT /note="Macrocin O-methyltransferase"
FT /id="PRO_0000418455"
FT ACT_SITE 65
FT /note="Proton acceptor"
FT /evidence="ECO:0000255"
FT BINDING 57..58
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9L9F2"
FT BINDING 85..89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9L9F2"
FT BINDING 115..119
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9L9F2"
FT BINDING 173
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9L9F2"
FT BINDING 191..192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9L9F2"
FT BINDING 191
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT BINDING 218
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT BINDING 219
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT CONFLICT 91..93
FT /note="GGA -> AP (in Ref. 2; AAD12168)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 256 AA; 28696 MW; 3BCE5E7F56237F90 CRC64;
MAPSPDHARD LYIELLKKVV SNVIYEDPTH VAGMITDASF DRTSRESGED YPTVAHTMIG
LKRLDNLHRC LADVVEDGVP GDFIETGVWR GGACIFARGL LNAYGQADRT VWVADSFQGF
PELTGSDHPL DVEIDLHQYN EAVDLPTSEE TVRENFARYG LLDDNVRFLA GWFKDTMPAA
PVKQLAVMRL DGDSYGATMD VLDSLYERLS PGGYVIVDDY CIPACREAVH DFRDRLGIRD
TIHRIDRQGA YWRHSG
