NOVL_STRNV
ID NOVL_STRNV Reviewed; 527 AA.
AC Q9L9F6;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=8-demethylnovobiocic acid synthase;
DE EC=6.3.1.15;
DE AltName: Full=8-demethylnovobiocic acid synthetase;
DE AltName: Full=Novobiocic acid synthetase;
DE AltName: Full=Novobiocin biosynthesis protein L;
DE AltName: Full=Novobiocin ligase;
GN Name=novL;
OS Streptomyces niveus (Streptomyces spheroides).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=193462;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC 2449;
RX PubMed=10770754; DOI=10.1128/aac.44.5.1214-1222.2000;
RA Steffensky M., Muhlenweg A., Wang Z.X., Li S.M., Heide L.;
RT "Identification of the novobiocin biosynthetic gene cluster of Streptomyces
RT spheroides NCIB 11891.";
RL Antimicrob. Agents Chemother. 44:1214-1222(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP PATHWAY, AND SUBUNIT.
RC STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC 2449;
RX PubMed=10801869; DOI=10.1074/jbc.m003066200;
RA Steffensky M., Li S.M., Heide L.;
RT "Cloning, overexpression, and purification of novobiocic acid synthetase
RT from Streptomyces spheroides NCIMB 11891.";
RL J. Biol. Chem. 275:21754-21760(2000).
RN [3]
RP FUNCTION.
RC STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC 2449;
RX PubMed=15218104; DOI=10.1073/pnas.0403526101;
RA Pi N., Meyers C.L., Pacholec M., Walsh C.T., Leary J.A.;
RT "Mass spectrometric characterization of a three-enzyme tandem reaction for
RT assembly and modification of the novobiocin skeleton.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10036-10041(2004).
CC -!- FUNCTION: Catalyzes the formation of an amide bond between 3-
CC dimethylallyl-4-hydroxybenzoate (ring A of novobiocin) and 3-amino-4,7-
CC dihydroxycoumarin (ring B of novobiocin) in an ATP-dependent reaction
CC in the novobiocin biosynthesis pathway. Novobiocin is an aminocoumarin
CC family antibiotic that targets bacterial DNA gyrases.
CC {ECO:0000269|PubMed:10801869, ECO:0000269|PubMed:15218104}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-amino-4,7-dihydroxycoumarin + 3-dimethylallyl-4-
CC hydroxybenzoate + ATP = 8-desmethylnovobiocic acid + AMP +
CC diphosphate; Xref=Rhea:RHEA:36699, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:73954, ChEBI:CHEBI:74155,
CC ChEBI:CHEBI:74156, ChEBI:CHEBI:456215; EC=6.3.1.15;
CC Evidence={ECO:0000269|PubMed:10801869};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10801869};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:10801869};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=19 uM for 3-dimethylallyl-4-hydroxybenzoate
CC {ECO:0000269|PubMed:10801869};
CC KM=131 uM for 3-amino-4,7-dihydroxycoumarin
CC {ECO:0000269|PubMed:10801869};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:10801869};
CC -!- PATHWAY: Antibiotic biosynthesis; novobiocin biosynthesis.
CC {ECO:0000269|PubMed:10801869}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10801869}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF170880; AAF67505.1; -; Genomic_DNA.
DR RefSeq; WP_069626142.1; NZ_MDCR01000039.1.
DR AlphaFoldDB; Q9L9F6; -.
DR SMR; Q9L9F6; -.
DR KEGG; ag:AAF67505; -.
DR BioCyc; MetaCyc:MON-18056; -.
DR BRENDA; 6.3.1.15; 6099.
DR SABIO-RK; Q9L9F6; -.
DR UniPathway; UPA01035; -.
DR GO; GO:0102527; F:8-demethylnovobiocate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016880; F:acid-ammonia (or amide) ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IDA:UniProtKB.
DR GO; GO:0043642; P:novobiocin biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; ATP-binding; Ligase; Magnesium; Manganese;
KW Nucleotide-binding.
FT CHAIN 1..527
FT /note="8-demethylnovobiocic acid synthase"
FT /id="PRO_0000423998"
FT BINDING 180..188
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 312..317
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 397
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 503
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 527 AA; 56921 MW; C19F1B702E099E94 CRC64;
MANKDHAPEH YVTRILAEAT LDGARPVVRW RDTVITGTQL DRSVRRVVTA LREAGVARDH
AVAVLTQVNS PWMLIVRYAA HLVGASVVYI TGANHGIVTH ELPVATRVRM LREAGASVLV
FDESNAQLAE TVDETVRDKL VLCGLGHPAS GTVSVDGRPV DDVSVDFTPE APELAMVLYT
SGTTGQPKGV CRSFGSWNAA ALRGAAYPRP VFLTMTAVSQ TVAMIVDTVL AAGGSVLLRE
RFDPADFLRD VGEHRVTETF MGVAQLYAIL GHPDARTADL SSLRHVLYLG CPASPERLRE
AAALLPGVLA QSYGSTEAGR ITVLRAADHE RPELLATVGR AVPGVTIAIR DPETGHDLPV
GEIGEVVVHG PEVMAGYVAD PEHTARVIRD GWVHTGDFGS VDERGYVRLF GRMREVVKVQ
DTRVSPTEVE KVLVGCPGVV DACVYGHRGP DLIEELHAAV VLGTEGAPSF DTLRDHVARA
MTPTHAPIRF VRWRRFPINN TGKVNRLRVR EVSAEARGDS PDVLVDR
