CMLP_STRVP
ID CMLP_STRVP Reviewed; 963 AA.
AC F2RB81;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Non-ribosomal peptide synthetase CmlP {ECO:0000305};
DE EC=6.2.1.- {ECO:0000269|PubMed:17520135};
GN Name=cmlP {ECO:0000303|PubMed:11577160};
GN OrderedLocusNames=SVEN_0922 {ECO:0000312|EMBL:CCA54209.1};
OS Streptomyces venezuelae (strain ATCC 10712 / CBS 650.69 / DSM 40230 / JCM
OS 4526 / NBRC 13096 / PD 04745).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=953739;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10712 / CBS 650.69 / DSM 40230 / JCM 4526 / NBRC 13096 / PD
RC 04745;
RX PubMed=21463507; DOI=10.1186/1471-2164-12-175;
RA Pullan S.T., Chandra G., Bibb M.J., Merrick M.;
RT "Genome-wide analysis of the role of GlnR in Streptomyces venezuelae
RT provides new insights into global nitrogen regulation in actinomycetes.";
RL BMC Genomics 12:175-175(2011).
RN [2]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 10712 / CBS 650.69 / DSM 40230 / JCM 4526 / NBRC 13096 / PD
RC 04745;
RX PubMed=11577160; DOI=10.1099/00221287-147-10-2817;
RA He J., Magarvey N., Piraee M., Vining L.C.;
RT "The gene cluster for chloramphenicol biosynthesis in Streptomyces
RT venezuelae ISP5230 includes novel shikimate pathway homologues and a
RT monomodular non-ribosomal peptide synthetase gene.";
RL Microbiology 147:2817-2829(2001).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP DOMAIN.
RX PubMed=17520135; DOI=10.1039/b703356g;
RA Pacholec M., Sello J.K., Walsh C.T., Thomas M.G.;
RT "Formation of an aminoacyl-S-enzyme intermediate is a key step in the
RT biosynthesis of chloramphenicol.";
RL Org. Biomol. Chem. 5:1692-1694(2007).
CC -!- FUNCTION: Involved in chloramphenicol biosynthesis (PubMed:11577160).
CC Activates 4-amino-L-phenylalanine by adenylation and loads it onto its
CC peptidyl carrier domain, via a thioester linkage to the
CC phosphopanthetheine moiety (PubMed:17520135). Can also adenylate
CC tyrosine and phenylalanine at low rates, but not L-p-nitrophenylalanine
CC or threo-phenylserine (PubMed:17520135). {ECO:0000269|PubMed:11577160,
CC ECO:0000269|PubMed:17520135}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-amino-L-phenylalanine + ATP + holo-[peptidyl-carrier
CC protein] = 4-amino-L-phenylalanyl-[peptidyl-carrier protein] + AMP +
CC diphosphate; Xref=Rhea:RHEA:59436, Rhea:RHEA-COMP:11480, Rhea:RHEA-
CC COMP:15237, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:142855, ChEBI:CHEBI:143072, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:17520135};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59437;
CC Evidence={ECO:0000269|PubMed:17520135};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:P0C061};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:P0C061};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.90 mM for 4-amino-L-phenylalanine {ECO:0000269|PubMed:17520135};
CC KM=4.10 mM for L-tyrosine {ECO:0000269|PubMed:17520135};
CC KM=9.40 mM for L-phenylalanine {ECO:0000269|PubMed:17520135};
CC Note=kcat is 7.3 min(-1) for adenylation of 4-amino-L-phenylalanine.
CC kcat is 1.97 min(-1) for adenylation of L-tyrosine. kcat is 0.90
CC min(-1) for adenylation of L-phenylalanine.
CC {ECO:0000269|PubMed:17520135};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:11577160,
CC ECO:0000269|PubMed:17520135}.
CC -!- DOMAIN: Contains an N-terminal adenylation domain, an internal peptidyl
CC carrier domain and a C-terminal domain that is homologous to
CC nicotinamide-dependent dehydrogenases. {ECO:0000305|PubMed:17520135}.
CC -!- DISRUPTION PHENOTYPE: Disruption mutant does not produce
CC chloramphenicol. Mutant does not accumulate 4-amino-L-phenylalanine.
CC {ECO:0000269|PubMed:11577160}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; FR845719; CCA54209.1; -; Genomic_DNA.
DR AlphaFoldDB; F2RB81; -.
DR SMR; F2RB81; -.
DR STRING; 953739.SVEN_0922; -.
DR EnsemblBacteria; CCA54209; CCA54209; SVEN_0922.
DR KEGG; sve:SVEN_0922; -.
DR PATRIC; fig|953739.5.peg.2968; -.
DR eggNOG; COG1020; Bacteria.
DR HOGENOM; CLU_000022_2_17_11; -.
DR OMA; ENDKFTM; -.
DR BioCyc; MetaCyc:MON-20703; -.
DR Proteomes; UP000006854; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF01370; Epimerase; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; ATP-binding; Ligase; Nucleotide-binding;
KW Phosphopantetheine; Phosphoprotein; Reference proteome.
FT CHAIN 1..963
FT /note="Non-ribosomal peptide synthetase CmlP"
FT /id="PRO_0000447247"
FT DOMAIN 492..568
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 928..963
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 526
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 963 AA; 102318 MW; 036FF280597D9067 CRC64;
MVELPDLLTD LFRRHRGRTA LRTAGRTWTY EELDRVTSAL ARRIDAECPA GRRVLVAGEH
TAEAVVWALA AMRSHAVHTP MNPGLPADRF EEFARVADAA LLVCFEREAL VRGEKAGLRA
LYAGDVGWPT DPAPAPADGT ADEPARSRVA YSIFTSGSTG DPKLVDVGHG GLLNLCRSLR
RLLDITPDDQ VLHFASLSFD ASVSEILGTL YAGATLVVPV RDQASWLGSV SRHLAAHGCD
LAMLSPSVYA RLDEAARSRI RKVEFCGEAL GEGEYDKAAR YSRVFNAYGP TEATVCFSLA
ELTSYTPSIG TPVDGFRAYV RDPDSGDHAT AGTGELVIVG DGVALGYAGG SPAENEVFGT
VDGSPAYATG DVVSLSDDGE LTYLGRIDEQ IKRLGHRVNL AHVGSTLSRH LGREVALVRQ
DATILLVTAA DGEATEESLM ARIRDLVPVW EAPDRLVLVD ALPLTSGGKV DRSALRELLA
SPAGAPHGGT DGEDAAELRR VLDVVTAVLG QEIGPETSIF DAGGSSLAMI QIQVKLSDAY
GEEAVEAAFA AMDYDFAPAA FLRHLRGEAV APAESAVDTL LRRVETERDA LRAELPLLRR
DTRHEPVPGA ADGDREVLLT GASGFIGGHV LDRLLAAGRP VLVVSTGDPD GVLTGHATRF
GRQAADYARV RAISYAELER WVDRRRGPVV DAVVHCGYQV NHLLPLDSHL SGSVRNTALV
VRAAAALGAR SFAFLSAASA GADFLPLSAA TLTAVGDPYS RSKLISEEYV NTLAVLGCAV
SHYRPGLVYG HRPEDRHHLK DDWFTALLET ARRVGAMPRL SGHVPVCDVG TLADTLLGRP
DANPGTADGA SRTPDSRSAV VVHRTYALDE LLRHTGLTEA DVLAPAAWFE RVRDGGEVPA
PLLAAMQAAL SGPGWPSAHR EVDHDILGRL LGTPPDTPAG DRPERTGTTA EAQNGAAHAP
TPR
