DPGA_AMYBA
ID DPGA_AMYBA Reviewed; 372 AA.
AC Q939X3;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 70.
DE RecName: Full=3,5-dihydroxyphenylacetyl-CoA synthase {ECO:0000303|PubMed:11495926};
DE EC=2.3.1.246 {ECO:0000269|PubMed:11495926, ECO:0000269|PubMed:14744141};
DE AltName: Full=3,5-dihydroxyphenylacetyl-CoA synthase polyketide synthase type III {ECO:0000305};
GN Name=dpgA {ECO:0000303|PubMed:11495926};
OS Amycolatopsis balhimycina.
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Amycolatopsis.
OX NCBI_TaxID=208443;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 5908;
RX PubMed=10390204; DOI=10.1128/aac.43.7.1565;
RA Pelzer S., Sussmuth R., Heckmann D., Recktenwald J., Huber P., Jung G.,
RA Wohlleben W.;
RT "Identification and analysis of the balhimycin biosynthetic gene cluster
RT and its use for manipulating glycopeptide biosynthesis in Amycolatopsis
RT mediterranei DSM5908.";
RL Antimicrob. Agents Chemother. 43:1565-1573(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 5908;
RX PubMed=12404385;
RX DOI=10.1002/1521-3773(20011217)40:24<4688::aid-anie4688>3.0.co;2-m;
RA Bischoff D., Pelzer S., Bister B., Nicholson G.J., Stockert S., Schirle M.,
RA Wohlleben W., Jung G., Suessmuth R.D.;
RT "The biosynthesis of vancomycin-type glycopeptide antibiotics - the order
RT of cyclization steps.";
RL Angew. Chem. Int. Ed. Engl. 40:4688-4691(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=DSM 5908;
RX PubMed=11495926; DOI=10.1074/jbc.m106580200;
RA Pfeifer V., Nicholson G.J., Ries J., Recktenwald J., Schefer A.B.,
RA Shawky R.M., Schroeder J., Wohlleben W., Pelzer S.;
RT "A polyketide synthase in glycopeptide biosynthesis: the biosynthesis of
RT the non-proteinogenic amino acid (S)-3,5-dihydroxyphenylglycine.";
RL J. Biol. Chem. 276:38370-38377(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 5908;
RX PubMed=11880037; DOI=10.1016/s1074-5521(02)00101-1;
RA Puk O., Huber P., Bischoff D., Recktenwald J., Jung G., Suessmuth R.D.,
RA van Pee K.H., Wohlleben W., Pelzer S.;
RT "Glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908: function
RT of a halogenase and a haloperoxidase/perhydrolase.";
RL Chem. Biol. 9:225-235(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 5908;
RX PubMed=11932455; DOI=10.1099/00221287-148-4-1105;
RA Recktenwald J., Shawky R.M., Puk O., Pfennig F., Keller U., Wohlleben W.,
RA Pelzer S.;
RT "Nonribosomal biosynthesis of vancomycin-type antibiotics: a heptapeptide
RT backbone and eight peptide synthetase modules.";
RL Microbiology 148:1105-1118(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP CYS-160; CYS-190 AND HIS-296, AND REACTION MECHANISM.
RX PubMed=14744141; DOI=10.1021/bi035714b;
RA Tseng C.C., McLoughlin S.M., Kelleher N.L., Walsh C.T.;
RT "Role of the active site cysteine of DpgA, a bacterial type III polyketide
RT synthase.";
RL Biochemistry 43:970-980(2004).
CC -!- FUNCTION: Involved in the biosynthesis of the nonproteinogenic amino
CC acid monomer (S)-3,5-dihydroxyphenylglycine (Dpg) responsible of the
CC production of balhimycin antibiotic (PubMed:11495926). Catalyzes the
CC Claisen condensation of four molecules of malonyl-CoA to yield 3,5-
CC dihydroxyphenylacetyl-CoA (DPA-CoA) and three free coenzyme A (CoA).
CC DpgA requires the presence of the dehydratases DpgB and DpgD to
CC facilitate the aromatization of the DPA-S-DgpA or DPA-S-CoA
CC intermediate. {ECO:0000269|PubMed:11495926,
CC ECO:0000269|PubMed:14744141}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 H(+) + 4 malonyl-CoA = (3,5-dihydroxyphenyl)acetyl-CoA + 4
CC CO2 + 3 CoA + H2O; Xref=Rhea:RHEA:44744, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:84554; EC=2.3.1.246;
CC Evidence={ECO:0000269|PubMed:11495926, ECO:0000269|PubMed:14744141};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 uM for malonyl-CoA {ECO:0000269|PubMed:14744141};
CC Note=kcat is 0.81 min(-1) for transferase activity with malonyl-CoA
CC as substrate. {ECO:0000269|PubMed:14744141};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:11495926}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to produce
CC balhimycin. {ECO:0000269|PubMed:11495926}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene
CC synthases family. {ECO:0000305}.
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DR EMBL; Y16952; CAC48378.1; -; Genomic_DNA.
DR AlphaFoldDB; Q939X3; -.
DR SMR; Q939X3; -.
DR KEGG; ag:CAC48378; -.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IDA:UniProtKB.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR012328; Chalcone/stilbene_synt_C.
DR InterPro; IPR001099; Chalcone/stilbene_synt_N.
DR InterPro; IPR011141; Polyketide_synthase_type-III.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR11877; PTHR11877; 1.
DR Pfam; PF02797; Chal_sti_synt_C; 1.
DR Pfam; PF00195; Chal_sti_synt_N; 1.
DR PIRSF; PIRSF000451; PKS_III; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; Transferase.
FT CHAIN 1..372
FT /note="3,5-dihydroxyphenylacetyl-CoA synthase"
FT /id="PRO_0000435603"
FT ACT_SITE 160
FT /evidence="ECO:0000305|PubMed:14744141"
FT MUTAGEN 160
FT /note="C->A: Reduces the formation of DPA-CoA. Strong
FT decrease of the affinity for malonyl-CoA."
FT /evidence="ECO:0000269|PubMed:14744141"
FT MUTAGEN 160
FT /note="C->S: Reduces the formation of DPA-CoA. Slight
FT decrease of the affinity for malonyl-CoA."
FT /evidence="ECO:0000269|PubMed:14744141"
FT MUTAGEN 190
FT /note="C->A: Produces DPA-CoA at the same level as the
FT wild-type."
FT /evidence="ECO:0000269|PubMed:14744141"
FT MUTAGEN 296
FT /note="H->A: Reduces the formation of DPA-CoA."
FT /evidence="ECO:0000269|PubMed:14744141"
SQ SEQUENCE 372 AA; 39491 MW; B263CDD46A00BBD7 CRC64;
MGVDVSMTTS IEPAEDLSVL SGLTEITRFA GVGTAVSASS YSQSEVLDIL DVEDPKIRSV
FLNSAIDRRF LTLPPESPGG GRVSEPQGDL LDKHKELAVD MGCRALEACL KSAGATLSDL
RHLCCVTSTG FLTPGLSALI IRELGIDPHC SRSDIVGMGC NAGLNALNVV AGWSAAHPGE
LGVVLCSEAC SAAYALDGTM RTAVVNSLFG DGSAALAVIS GDGRVPGPRV LKFASYIITD
ALDAMRYDWD RDQDRFSFFL DPQIPYVVGA HAEIVADRLL SGTGLRRSDI GHWLVHSGGK
KVIDSVVVNL GLSRHDVRHT TGVLRDYGNL SSGSFLFSYE RLAEEGVTRP GDYGVLMTMG
PGSTIEMALI QW
