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Monoogygenase tpcG (EC 1.-.-.-) (Trypacidin synthesis protein G)

 TPCG_ASPFU              Reviewed;         263 AA.
07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
05-JUL-2005, sequence version 1.
05-DEC-2018, entry version 66.
RecName: Full=Monoogygenase tpcG {ECO:0000303|PubMed:26242966};
EC=1.-.-.- {ECO:0000305|PubMed:26242966};
AltName: Full=Trypacidin synthesis protein G {ECO:0000303|PubMed:26242966};
Name=tpcG {ECO:0000303|PubMed:26242966};
Synonyms=tynG {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14520;
Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
A1100) (Aspergillus fumigatus).
Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
PubMed=16372009; DOI=10.1038/nature04332;
Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S.,
Arroyo J., Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W.,
Bowyer P., Chen D., Collins M., Coulsen R., Davies R., Dyer P.S.,
Farman M.L., Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R.,
Fosker N., Fraser A., Garcia J.L., Garcia M.J., Goble A.,
Goldman G.H., Gomi K., Griffith-Jones S., Gwilliam R., Haas B.J.,
Haas H., Harris D.E., Horiuchi H., Huang J., Humphray S., Jimenez J.,
Keller N., Khouri H., Kitamoto K., Kobayashi T., Konzack S.,
Kulkarni R., Kumagai T., Lafton A., Latge J.-P., Li W., Lord A.,
Lu C., Majoros W.H., May G.S., Miller B.L., Mohamoud Y., Molina M.,
Monod M., Mouyna I., Mulligan S., Murphy L.D., O'Neil S., Paulsen I.,
Penalva M.A., Pertea M., Price C., Pritchard B.L., Quail M.A.,
Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
Ronning C.M., Rutter S., Salzberg S.L., Sanchez M.,
Sanchez-Ferrero J.C., Saunders D., Seeger K., Squares R., Squares S.,
Takeuchi M., Tekaia F., Turner G., Vazquez de Aldana C.R., Weidman J.,
White O., Woodward J.R., Yu J.-H., Fraser C.M., Galagan J.E., Asai K.,
Machida M., Hall N., Barrell B.G., Denning D.W.;
"Genomic sequence of the pathogenic and allergenic filamentous fungus
Aspergillus fumigatus.";
Nature 438:1151-1156(2005).
PubMed=22319557; DOI=10.1371/journal.pone.0029906;
Gauthier T., Wang X., Sifuentes Dos Santos J., Fysikopoulos A.,
Tadrist S., Canlet C., Artigot M.P., Loiseau N., Oswald I.P., Puel O.;
"Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is
cytotoxic to lung cells.";
PLoS ONE 7:E29906-E29906(2012).
PubMed=26278536; DOI=10.1007/s00253-015-6898-1;
Mattern D.J., Schoeler H., Weber J., Novohradska S., Kraibooj K.,
Dahse H.M., Hillmann F., Valiante V., Figge M.T., Brakhage A.A.;
"Identification of the antiphagocytic trypacidin gene cluster in the
human-pathogenic fungus Aspergillus fumigatus.";
Appl. Microbiol. Biotechnol. 99:10151-10161(2015).
PubMed=26242966; DOI=10.1111/1462-2920.13007;
Throckmorton K., Lim F.Y., Kontoyiannis D.P., Zheng W., Keller N.P.;
"Redundant synthesis of a conidial polyketide by two distinct
secondary metabolite clusters in Aspergillus fumigatus.";
Environ. Microbiol. 18:246-259(2016).
-!- FUNCTION: Monooxygenase; part of the gene cluster that mediates
the biosynthesis of trypacidin, a mycotoxin with antiprotozoal
activity and that plays a role in the infection process
(PubMed:26278536, PubMed:26242966). The pathway begins with the
synthesis of atrochrysone thioester by the polyketide synthase
(PKS) tpcC (PubMed:26242966). The atrochrysone carboxyl ACP
thioesterase tpcB then breaks the thioester bond and releases the
atrochrysone carboxylic acid from tpcC (PubMed:26242966). The
decarboxylase tpcK converts atrochrysone carboxylic acid to
atrochrysone which is further reduced into emodin anthrone
(PubMed:26242966). The next step is performed by the emodin
anthrone oxygenase tpcL that catalyzes the oxidation of
emodinanthrone to emodin (PubMed:26242966). Emodin O-
methyltransferase encoded by tpcA catalyzes methylation of the 8-
hydroxy group of emodin to form questin (PubMed:26242966). Ring
cleavage of questin by questin oxidase tpcI leads to
desmethylsulochrin via several intermediates including questin
epoxide (By similarity). Another methylation step catalyzed by
tpcM leads to the formation of sulochrin which is further
converted to monomethylsulfochrin by tpcH. Finally, the tpcJ
catalyzes the conversion of monomethylsulfochrin to trypacidin
(PubMed:26242966). Trypacidin is toxic for human pulmonary and
bronchial epithelial cells by initiating the intracellular
formation of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)),
thus triggering host necrotic cell death (PubMed:22319557). The
trypacidin pathway is also able to produce endocrocin via a
distinct route from the endocrocin Enc pathway (PubMed:26242966).
{ECO:0000250|UniProtKB:Q0CCX9, ECO:0000269|PubMed:22319557,
ECO:0000269|PubMed:26242966, ECO:0000269|PubMed:26278536}.
-!- PATHWAY: Secondary metabolite biosynthesis.
-!- TISSUE SPECIFICITY: Specifically expressed in conidia
(PubMed:22319557). {ECO:0000305|PubMed:22319557}.
-!- SIMILARITY: Belongs to the avfA family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; AAHF01000005; EAL89343.1; -; Genomic_DNA.
RefSeq; XP_751381.1; XM_746288.1.
ProteinModelPortal; Q4WQZ1; -.
EnsemblFungi; EAL89343; EAL89343; AFUA_4G14520.
GeneID; 3509605; -.
KEGG; afm:AFUA_4G14520; -.
EuPathDB; FungiDB:Afu4g14520; -.
HOGENOM; HOG000216811; -.
InParanoid; Q4WQZ1; -.
OrthoDB; EOG092C4PZ1; -.
Proteomes; UP000002530; Chromosome 4.
Proteomes; UP000002530; Unassembled WGS sequence.
GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
GO; GO:0044550; P:secondary metabolite biosynthetic process; IGC:AspGD.
InterPro; IPR016040; NAD(P)-bd_dom.
InterPro; IPR036291; NAD(P)-bd_dom_sf.
Pfam; PF13460; NAD_binding_10; 1.
SUPFAM; SSF51735; SSF51735; 1.
2: Evidence at transcript level;
Complete proteome; Monooxygenase; Oxidoreductase; Reference proteome.
CHAIN 1 263 Monoogygenase tpcG.
SEQUENCE 263 AA; 29017 MW; FBA39712BD3CE684 CRC64;

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