ID   PPTA_ASPFU              Reviewed;         359 AA.
AC   Q4X1W0; E9R469; Q4FCS5;
DT   20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 1.
DT   25-MAY-2022, entry version 86.
DE   RecName: Full=4'-phosphopantetheinyl transferase A {ECO:0000303|PubMed:12664133};
DE            Short=PPTase A {ECO:0000303|PubMed:12664133};
DE            EC=2.7.8.7 {ECO:0000269|PubMed:21195204, ECO:0000269|PubMed:28720735};
DE   AltName: Full=Acyl-carrier-protein synthase pptA {ECO:0000303|PubMed:21195204};
DE   AltName: Full=Phosphopantetheine:protein transferase pptA {ECO:0000303|PubMed:21195204};
GN   Name=pptA {ECO:0000303|PubMed:21195204}; ORFNames=AFUA_2G08590;
OS   Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS   A1100) (Aspergillus fumigatus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=330879;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX   PubMed=12664133; DOI=10.1007/s00294-003-0382-7;
RA   Keszenman-Pereyra D., Lawrence S., Twfieg M.E., Price J., Turner G.;
RT   "The npgA/cfwA gene encodes a putative 4'-phosphopantetheinyl transferase
RT   which is essential for penicillin biosynthesis in Aspergillus nidulans.";
RL   Curr. Genet. 43:186-190(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Keszenman-Pereyra D., Zucchi T.D., Haas H., Turner G.;
RT   "The gene pptA, homolog of npgA, is not an essential gene in Aspergillus
RT   fumigatus.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX   PubMed=16372009; DOI=10.1038/nature04332;
RA   Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA   Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA   Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA   Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA   Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA   Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA   Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA   Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA   Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA   Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA   O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA   Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA   Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA   Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA   Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA   Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA   Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA   Barrell B.G., Denning D.W.;
RT   "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT   Aspergillus fumigatus.";
RL   Nature 438:1151-1156(2005).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=21195204; DOI=10.1016/j.fgb.2010.12.006;
RA   Allen G., Bromley M., Kaye S.J., Keszenman-Pereyra D., Zucchi T.D.,
RA   Price J., Birch M., Oliver J.D., Turner G.;
RT   "Functional analysis of a mitochondrial phosphopantetheinyl transferase
RT   (PPTase) gene pptB in Aspergillus fumigatus.";
RL   Fungal Genet. Biol. 48:456-464(2011).
RN   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP   AND BIOTECHNOLOGY.
RX   PubMed=28720735; DOI=10.1128/mbio.01504-16;
RA   Johns A., Scharf D.H., Gsaller F., Schmidt H., Heinekamp T.,
RA   Strassburger M., Oliver J.D., Birch M., Beckmann N., Dobb K.S.,
RA   Gilsenan J., Rash B., Bignell E., Brakhage A.A., Bromley M.J.;
RT   "A nonredundant phosphopantetheinyl transferase, PptA, is a novel
RT   antifungal target that directs secondary metabolite, siderophore, and
RT   lysine biosynthesis in Aspergillus fumigatus and is critical for
RT   pathogenicity.";
RL   MBio 8:0-0(2017).
CC   -!- FUNCTION: Acyl-carrier-protein synthase that transfers the 4'-
CC       phosphopantetheine moiety from coenzyme A to a Ser of an acyl-carrier-
CC       protein (PubMed:12664133, PubMed:21195204, PubMed:28720735). The 4'-
CC       phosphopantetheine (4'-PPT) portion of CoA provides the essential
CC       prosthetic group for a number of carrier proteins and multi-domain
CC       enzymes, priming them for the acceptance of acyl building blocks in
CC       fatty acid synthesis and many aspects of secondary metabolism mediated
CC       by polyketide synthases (PKSs) and non-ribosomal peptide synthetases
CC       (NRPSs) (PubMed:21195204, PubMed:28720735). PptA is able to transfer
CC       the cofactor to a broad range of enzymes with acyl- or peptidyl-carrier
CC       protein domains and activates target enzymes involved in the synthesis
CC       of lysine, but also secondary metabolites including gliotoxin,
CC       fumigaclavine C, fumiquinazole A, fumiquinazoline C, pyripyroprene A,
CC       fumagillin, the siderophores triacetylfusarinine C (TAFC) and
CC       ferricrocin (FC), and dihydroxy naphthalene (DHN)-melanin
CC       (PubMed:21195204, PubMed:28720735). Plays an essential role in
CC       virulence (PubMed:28720735). {ECO:0000269|PubMed:21195204,
CC       ECO:0000269|PubMed:28720735, ECO:0000305|PubMed:12664133}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=apo-[ACP] + CoA = adenosine 3',5'-bisphosphate + H(+) + holo-
CC         [ACP]; Xref=Rhea:RHEA:12068, Rhea:RHEA-COMP:9685, Rhea:RHEA-
CC         COMP:9690, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:58343, ChEBI:CHEBI:64479; EC=2.7.8.7;
CC         Evidence={ECO:0000269|PubMed:21195204, ECO:0000269|PubMed:28720735};
CC   -!- ACTIVITY REGULATION: Activity is inhibited bythe antifunfal copmpounds
CC       PD 404,182, 6-nitroso-1,2-benzopyrone, and calmidazolium chloride with
CC       IC(50) values of 3.9 uM, 35.2 uM, and 19.2 uM, respectively
CC       (PubMed:28720735). {ECO:0000269|PubMed:28720735}.
CC   -!- DISRUPTION PHENOTYPE: Leads to the loss of the green conidial pigment
CC       and decreased viability of conidia (PubMed:21195204). Impairs virulence
CC       in both insect and murine infection models (PubMed:28720735).
CC       {ECO:0000269|PubMed:21195204, ECO:0000269|PubMed:28720735}.
CC   -!- BIOTECHNOLOGY: PptA is a druggable target in Aspergillus species that
CC       can be targeted in a selective way (PubMed:28720735). Its combined role
CC       in both primary and secondary metabolism, encompassing multiple
CC       virulence determinants, makes it a very promising antifungal drug
CC       target candidate (PubMed:28720735). {ECO:0000269|PubMed:28720735}.
CC   -!- SIMILARITY: Belongs to the P-Pant transferase superfamily.
CC       {ECO:0000305}.
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DR   EMBL; DQ092864; AAY99391.1; -; Genomic_DNA.
DR   EMBL; AAHF01000001; EAL93155.1; -; Genomic_DNA.
DR   RefSeq; XP_755193.1; XM_750100.1.
DR   AlphaFoldDB; Q4X1W0; -.
DR   SMR; Q4X1W0; -.
DR   STRING; 746128.CADAFUBP00002395; -.
DR   EnsemblFungi; EAL93155; EAL93155; AFUA_2G08590.
DR   GeneID; 3513464; -.
DR   KEGG; afm:AFUA_2G08590; -.
DR   VEuPathDB; FungiDB:Afu2g08590; -.
DR   eggNOG; KOG0945; Eukaryota.
DR   HOGENOM; CLU_031126_1_1_1; -.
DR   InParanoid; Q4X1W0; -.
DR   OMA; RWYIDTR; -.
DR   OrthoDB; 960416at2759; -.
DR   Proteomes; UP000002530; Chromosome 2.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IDA:AspGD.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0140614; P:1,8-dihydroxynaphthalene-melanin biosynthetic process; IMP:PHI-base.
DR   GO; GO:1902086; P:fumagillin biosynthetic process; IMP:PHI-base.
DR   GO; GO:1900809; P:fumigaclavine C biosynthetic process; IMP:PHI-base.
DR   GO; GO:1900775; P:fumiquinazoline biosynthetic process; IMP:PHI-base.
DR   GO; GO:2001310; P:gliotoxin biosynthetic process; IMP:PHI-base.
DR   GO; GO:0009085; P:lysine biosynthetic process; IMP:PHI-base.
DR   GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IBA:GO_Central.
DR   GO; GO:1900551; P:N',N'',N'''-triacetylfusarinine C biosynthetic process; IMP:PHI-base.
DR   GO; GO:0043324; P:pigment metabolic process involved in developmental pigmentation; IMP:AspGD.
DR   Gene3D; 3.90.470.20; -; 2.
DR   InterPro; IPR008278; 4-PPantetheinyl_Trfase_dom.
DR   InterPro; IPR037143; 4-PPantetheinyl_Trfase_dom_sf.
DR   Pfam; PF01648; ACPS; 1.
DR   SUPFAM; SSF56214; SSF56214; 2.
PE   1: Evidence at protein level;
KW   Reference proteome; Transferase; Virulence.
FT   CHAIN           1..359
FT                   /note="4'-phosphopantetheinyl transferase A"
FT                   /id="PRO_0000444447"
SQ   SEQUENCE   359 AA;  39547 MW;  29E514A840018366 CRC64;
     MGSAQNERIP SLTRWYIDTR QLTVTNPSLP LLEALQPSDQ EAVKRFYHLR DRHMSLASNL
     LKYLFIHRSC CIPWNKISIS RTPDPHRRPC FIPSPALTEA TDEPIPGIEF NVSHQASLVA
     LAGTIIPQSH GASPNPTTVF ANPSPSSVPA PSVPQVGIDI TCVDERHART SSAPSTRDQL
     AGYVDIFAEV FSSRELDTIK NLGGRFPADA QDGEAVEYGL RLFYTYWALK EAYIKMTGEA
     LLAPWLRELE FTDVIAPEPA PAPGQGSAEN WGEPYTGVKI WLYGKRVEDV RIEVVAFETG
     YIFATAARGA GLGAESRPLS RDAGVAVSVD RWMHMEKIDI DRDIAPCATG VCQCTKKQP