ID FAA22_MYCTU Reviewed; 705 AA.
AC P9WQ61; L0TE13; P96283; Q7D6D9;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 27-NOV-2024, entry version 48.
DE RecName: Full=p-hydroxybenzoic acid--AMP ligase FadD22;
DE Short=p-HB--AMP ligase FadD22;
DE EC=6.2.1.50 {ECO:0000250|UniProtKB:Q7TXK7};
DE AltName: Full=p-hydroxybenzoic acid-AMP synthetase;
DE Short=p-HB-AMP synthetase;
GN Name=fadD22; OrderedLocusNames=Rv2948c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION IN THE BIOSYNTHESIS OF P-HYDROXYBENZOIC ACID-AMP, CATALYTIC
RP ACTIVITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20553505; DOI=10.1111/j.1742-464x.2010.07688.x;
RA Simeone R., Leger M., Constant P., Malaga W., Marrakchi H., Daffe M.,
RA Guilhot C., Chalut C.;
RT "Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis
RT of phthiocerol dimycocerosates and related compounds in Mycobacterium
RT tuberculosis.";
RL FEBS J. 277:2715-2725(2010).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Catalyzes the adenylation of p-hydroxybenzoic acid (pHBA) to
CC form p-hydroxybenzoic acid-AMP (pHBA-AMP), which is converted directly
CC to p-hydroxybenzoyl-S-FadD22 (pHBA-S-FAdD22) thioester intermediate in
CC a CoA-independent manner by attack of the phosphopantetheine thiol of
CC FadD22. Usually, this intermediate primes the biosynthesis of the
CC phenolphthiocerol (PPOL) by presenting the pHBA starter unit for
CC elongation by Pks15/1, but M.tuberculosis lacks Pks15/1 due to a
CC natural frameshift and thus is unable to produce PPOL.
CC {ECO:0000269|PubMed:20553505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=holo-[4-hydroxyphenylalkanoate synthase] + 4-hydroxybenzoate +
CC ATP = 4-hydroxyphenyl-[4-hydroxyphenylalkanoate synthase] + AMP +
CC diphosphate; Xref=Rhea:RHEA:54696, Rhea:RHEA-COMP:12684, Rhea:RHEA-
CC COMP:13969, ChEBI:CHEBI:17879, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:138321, ChEBI:CHEBI:456215;
CC EC=6.2.1.50; Evidence={ECO:0000250|UniProtKB:Q7TXK7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxybenzoate + ATP + H(+) = 4-hydroxybenzoyl-5'-AMP +
CC diphosphate; Xref=Rhea:RHEA:46692, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17879, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:86435; Evidence={ECO:0000269|PubMed:20553505};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46693;
CC Evidence={ECO:0000269|PubMed:20553505};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- DISRUPTION PHENOTYPE: Disruption of fadD22 abolishes the production of
CC PPOL. {ECO:0000269|PubMed:20553505}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45752.1; -; Genomic_DNA.
DR PIR; A70669; A70669.
DR RefSeq; NP_217464.1; NC_000962.3.
DR RefSeq; WP_003414884.1; NZ_NVQJ01000015.1.
DR AlphaFoldDB; P9WQ61; -.
DR SMR; P9WQ61; -.
DR STRING; 83332.Rv2948c; -.
DR SwissLipids; SLP:000001280; -.
DR PaxDb; 83332-Rv2948c; -.
DR DNASU; 887295; -.
DR GeneID; 887295; -.
DR KEGG; mtu:Rv2948c; -.
DR KEGG; mtv:RVBD_2948c; -.
DR TubercuList; Rv2948c; -.
DR eggNOG; COG0236; Bacteria.
DR eggNOG; COG0318; Bacteria.
DR InParanoid; P9WQ61; -.
DR OrthoDB; 9803968at2; -.
DR PhylomeDB; P9WQ61; -.
DR BRENDA; 6.2.1.50; 3445.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016878; F:acid-thiol ligase activity; IDA:MTBBASE.
DR GO; GO:0016874; F:ligase activity; IDA:MTBBASE.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009247; P:glycolipid biosynthetic process; IMP:MTBBASE.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0097041; P:phenolic phthiocerol biosynthetic process; IDA:MTBBASE.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR CDD; cd05919; BCL_like; 1.
DR FunFam; 3.30.300.30:FF:000042; Fatty-acid-CoA ligase FadD22; 1.
DR FunFam; 3.40.50.12780:FF:000055; Fatty-acid-CoA ligase FadD22; 1.
DR FunFam; 1.10.1200.10:FF:000007; Probable polyketide synthase pks17; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig_com.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR PANTHER; PTHR43352; ACETYL-COA SYNTHETASE; 1.
DR PANTHER; PTHR43352:SF1; P-HYDROXYBENZOIC ACID--AMP LIGASE FADD22; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Fatty acid metabolism; Ligase; Lipid metabolism; Phosphopantetheine;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..705
FT /note="p-hydroxybenzoic acid--AMP ligase FadD22"
FT /id="PRO_0000406350"
FT DOMAIN 541..619
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 579
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 705 AA; 75198 MW; 600F2D0EABFDF1DC CRC64;
MRNGNLAGLL AEQASEAGWY DRPAFYAADV VTHGQIHDGA ARLGEVLRNR GLSSGDRVLL
CLPDSPDLVQ LLLACLARGV MAFLANPELH RDDHALAARN TEPALVVTSD ALRDRFQPSR
VAEAAELMSE AARVAPGGYE PMGGDALAYA TYTSGTTGPP KAAIHRHADP LTFVDAMCRK
ALRLTPEDTG LCSARMYFAY GLGNSVWFPL ATGGSAVINS APVTPEAAAI LSARFGPSVL
YGVPNFFARV IDSCSPDSFR SLRCVVSAGE ALELGLAERL MEFFGGIPIL DGIGSTEVGQ
TFVSNRVDEW RLGTLGRVLP PYEIRVVAPD GTTAGPGVEG DLWVRGPAIA KGYWNRPDSP
VANEGWLDTR DRVCIDSDGW VTYRCRADDT EVIGGVNVDP REVERLIIED EAVAEAAVVA
VRESTGASTL QAFLVATSGA TIDGSVMRDL HRGLLNRLSA FKVPHRFAVV DRLPRTPNGK
LVRGALRKQS PTKPIWELSL TEPGSGVRAQ RDDLSASNMT IAGGNDGGAT LRERLVALRQ
ERQRLVVDAV CAEAAKMLGE PDPWSVDQDL AFSELGFDSQ MTVTLCKRLA AVTGLRLPET
VGWDYGSISG LAQYLEAELA GGHGRLKSAG PVNSGATGLW AIEEQLNKVE ELVAVIADGE
KQRVADRLRA LLGTIAGSEA GLGKLIQAAS TPDEIFQLID SELGK
//
