FAA26_MYCTU
ID FAA26_MYCTU Reviewed; 583 AA.
AC P9WQ43; L0TDT5; Q10976;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 37.
DE RecName: Full=Long-chain-fatty-acid--AMP ligase FadD26 {ECO:0000305};
DE Short=FAAL;
DE EC=6.2.1.59 {ECO:0000269|PubMed:15042094, ECO:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
DE AltName: Full=Acyl-AMP synthetase;
DE AltName: Full=FAAL26 {ECO:0000303|PubMed:19182784};
GN Name=fadD26; OrderedLocusNames=Rv2930; ORFNames=MTCY338.19;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; 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 PHTHIOCEROL, PATHWAY, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11279114; DOI=10.1074/jbc.m100662200;
RA Camacho L.R., Constant P., Raynaud C., Laneelle M.A., Triccas J.A.,
RA Gicquel B., Daffe M., Guilhot C.;
RT "Analysis of the phthiocerol dimycocerosate locus of Mycobacterium
RT tuberculosis. Evidence that this lipid is involved in the cell wall
RT permeability barrier.";
RL J. Biol. Chem. 276:19845-19854(2001).
RN [3]
RP FUNCTION AS AN ACYL-AMP SYNTHETASE, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15042094; DOI=10.1038/nature02384;
RA Trivedi O.A., Arora P., Sridharan V., Tickoo R., Mohanty D., Gokhale R.S.;
RT "Enzymic activation and transfer of fatty acids as acyl-adenylates in
RT mycobacteria.";
RL Nature 428:441-445(2004).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15749014; DOI=10.1016/j.molcel.2005.02.009;
RA Trivedi O.A., Arora P., Vats A., Ansari M.Z., Tickoo R., Sridharan V.,
RA Mohanty D., Gokhale R.S.;
RT "Dissecting the mechanism and assembly of a complex virulence mycobacterial
RT lipid.";
RL Mol. Cell 17:631-643(2005).
RN [5]
RP DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RC STRAIN=Mt103;
RX PubMed=15958066; DOI=10.1111/j.1365-2249.2005.02832.x;
RA Infante E., Aguilar L.D., Gicquel B., Pando R.H.;
RT "Immunogenicity and protective efficacy of the Mycobacterium tuberculosis
RT fadD26 mutant.";
RL Clin. Exp. Immunol. 141:21-28(2005).
RN [6]
RP CATALYTIC ACTIVITY.
RX PubMed=19182784; DOI=10.1038/nchembio.143;
RA Arora P., Goyal A., Natarajan V.T., Rajakumara E., Verma P., Gupta R.,
RA Yousuf M., Trivedi O.A., Mohanty D., Tyagi A., Sankaranarayanan R.,
RA Gokhale R.S.;
RT "Mechanistic and functional insights into fatty acid activation in
RT Mycobacterium tuberculosis.";
RL Nat. Chem. Biol. 5:166-173(2009).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20553505; DOI=10.1111/j.1742-4658.2010.07688.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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
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).
RN [9]
RP BIOTECHNOLOGY.
RX PubMed=31591165; DOI=10.1128/iai.00496-19;
RA Hernandez-Pando R., Shin S.J., Clark S., Casonato S., Becerril-Zambrano M.,
RA Kim H., Boldrin F., Mata-Espinoza D., Provvedi R., Arbues A.,
RA Marquina-Castillo B., Cioetto Mazzabo L., Barrios-Payan J., Martin C.,
RA Cho S.N., Williams A., Manganelli R.;
RT "Construction and characterization of the Mycobacterium tuberculosis sigE
RT fadD26 unmarked double mutant as a vaccine candidate.";
RL Infect. Immun. 88:0-0(2019).
CC -!- FUNCTION: Catalyzes the activation of long-chain fatty acids as acyl-
CC adenylates (acyl-AMP), which are then transferred to the
CC multifunctional polyketide synthase PpsA for further chain extension
CC (PubMed:15042094, PubMed:15749014, PubMed:20553505). Catalyzes the
CC adenylation of the long-chain fatty acids eicosanoate (C20) or
CC docosanoate (C22), and potentially the very-long-chain fatty acid
CC lignocerate (C24) (PubMed:15749014, PubMed:20553505). Involved in the
CC biosynthesis of phthiocerol dimycocerosate (DIM A) and phthiodiolone
CC dimycocerosate (DIM B) (PubMed:11279114, PubMed:20553505).
CC {ECO:0000269|PubMed:11279114, ECO:0000269|PubMed:15042094,
CC ECO:0000269|PubMed:15749014, ECO:0000269|PubMed:20553505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + holo-
CC [(phenol)carboxyphthiodiolenone synthase] = a long-chain fatty acyl-
CC [(phenol)carboxyphthiodiolenone synthase] + AMP + diphosphate;
CC Xref=Rhea:RHEA:64660, Rhea:RHEA-COMP:14271, Rhea:RHEA-COMP:16648,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57560,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:133243, ChEBI:CHEBI:456215;
CC EC=6.2.1.59; Evidence={ECO:0000269|PubMed:15042094,
CC ECO:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + eicosanoate + holo-[(phenol)carboxyphthiodiolenone
CC synthase] = AMP + diphosphate + icosanoyl-
CC [(phenol)carboxyphthiodiolenone synthase]; Xref=Rhea:RHEA:59156,
CC Rhea:RHEA-COMP:14271, Rhea:RHEA-COMP:14985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:32360, ChEBI:CHEBI:33019, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:87848, ChEBI:CHEBI:456215; EC=6.2.1.59;
CC Evidence={ECO:0000305|PubMed:15749014, ECO:0000305|PubMed:20553505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + docosanoate + holo-[(phenol)carboxyphthiodiolenone
CC synthase] = AMP + diphosphate + docosanoyl-
CC [(phenol)carboxyphthiodiolenone synthase]; Xref=Rhea:RHEA:59160,
CC Rhea:RHEA-COMP:14271, Rhea:RHEA-COMP:14987, ChEBI:CHEBI:23858,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:142238, ChEBI:CHEBI:456215; EC=6.2.1.59;
CC Evidence={ECO:0000305|PubMed:15749014, ECO:0000305|PubMed:20553505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dodecanoate + H(+) = diphosphate + dodecanoyl-AMP;
CC Xref=Rhea:RHEA:43712, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83623;
CC Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43713;
CC Evidence={ECO:0000269|PubMed:19182784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + hexadecanoate = diphosphate + hexadecanoyl-AMP;
CC Xref=Rhea:RHEA:43708, ChEBI:CHEBI:7896, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83627;
CC Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43709;
CC Evidence={ECO:0000269|PubMed:19182784};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:11279114, ECO:0000269|PubMed:20553505}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene abolishes the production
CC of phthiocerol dimycocerosate (DIM) on the cell envelope
CC (PubMed:11279114). Mutant is attenuated in BALB/c mice. Mutant induces
CC less pneumonia and larger delayed-type hypersensitivity (DTH)
CC reactions. It also induces lower but progressive production of IFN-
CC gamma, IL-4 and TNF-alpha (PubMed:15958066).
CC {ECO:0000269|PubMed:11279114, ECO:0000269|PubMed:15958066}.
CC -!- BIOTECHNOLOGY: Vaccination with the fadD26 mutant protects against
CC progressive tuberculosis more efficiently than does Bacille Calmette-
CC Guerin (BCG). It suggests that inactivation of DIM synthesis can
CC increase the immunogenicity of live vaccines, and increase their
CC ability to protect against tuberculosis, indicating that fadD26 mutant
CC could be a potential vaccine candidate (PubMed:15958066). A double
CC unmarked sigE fadD26 mutant is more attenuated and more protective than
CC BCG and is also a promising new prime TB vaccine candidate
CC (PubMed:31591165). {ECO:0000269|PubMed:15958066,
CC ECO:0000269|PubMed:31591165}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP45733.1; -; Genomic_DNA.
DR PIR; B70749; B70749.
DR RefSeq; NP_217446.2; NC_000962.3.
DR RefSeq; WP_003900597.1; NZ_NVQJ01000006.1.
DR AlphaFoldDB; P9WQ43; -.
DR SMR; P9WQ43; -.
DR STRING; 83332.Rv2930; -.
DR SwissLipids; SLP:000000985; -.
DR PaxDb; P9WQ43; -.
DR DNASU; 887603; -.
DR GeneID; 887603; -.
DR KEGG; mtu:Rv2930; -.
DR TubercuList; Rv2930; -.
DR eggNOG; COG0318; Bacteria.
DR OMA; AMRCESE; -.
DR PhylomeDB; P9WQ43; -.
DR Reactome; R-MTU-9635470; Dimycocersyl phthiocerol biosynthesis.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016878; F:acid-thiol ligase activity; IDA:MTBBASE.
DR GO; GO:0070566; F:adenylyltransferase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IMP:UniProtKB.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IDA:MTBBASE.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0097040; P:phthiocerol biosynthetic process; IDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IMP:MTBBASE.
DR CDD; cd05931; FAAL; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR040097; FAAL/FAAC.
DR Pfam; PF00501; AMP-binding; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..583
FT /note="Long-chain-fatty-acid--AMP ligase FadD26"
FT /id="PRO_0000193138"
SQ SEQUENCE 583 AA; 63044 MW; F97CD6E19E217435 CRC64;
MPVTDRSVPS LLQERADQQP DSTAYTYIDY GSDPKGFADS LTWSQVYSRA CIIAEELKLC
GLPGDRVAVL APQGLEYVLA FLGALQAGFI AVPLSTPQYG IHDDRVSAVL QDSKPVAILT
TSSVVGDVTK YAASHDGQPA PVVVEVDLLD LDSPRQMPAF SRQHTGAAYL QYTSGSTRTP
AGVIVSHTNV IANVTQSMYG YFGDPAKIPT GTVVSWLPLY HDMGLILGIC APLVARRRAM
LMSPMSFLRR PARWMQLLAT SGRCFSAAPN FAFELAVRRT SDQDMAGLDL RDVVGIVSGS
ERIHVATVRR FIERFAPYNL SPTAIRPSYG LAEATLYVAA PEAGAAPKTV RFDYEQLTAG
QARPCGTDGS VGTELISYGS PDPSSVRIVN PETMVENPPG VVGEIWVHGD HVTMGYWQKP
KQTAQVFDAK LVDPAPAAPE GPWLRTGDLG VISDGELFIM GRIKDLLIVD GRNHYPDDIE
ATIQEITGGR AAAIAVPDDI TEQLVAIIEF KRRGSTAEEV MLKLRSVKRE VTSAISKSHS
LRVADLVLVS PGSIPITTSG KIRRSACVER YRSDGFKRLD VAV
