AYG1_ASPFU
ID AYG1_ASPFU Reviewed; 406 AA.
AC Q4WZB3;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Heptaketide hydrolyase ayg1 {ECO:0000303|PubMed:11350964};
DE EC=3.7.1.- {ECO:0000269|PubMed:11350964};
DE AltName: Full=Conidial pigment biosynthesis protein ayg1 {ECO:0000305};
GN Name=ayg1 {ECO:0000303|PubMed:10515939}; ORFNames=AFUA_2G17550;
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 [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 [2]
RP FUNCTION.
RX PubMed=10515939; DOI=10.1128/jb.181.20.6469-6477.1999;
RA Tsai H.F., Wheeler M.H., Chang Y.C., Kwon-Chung K.J.;
RT "A developmentally regulated gene cluster involved in conidial pigment
RT biosynthesis in Aspergillus fumigatus.";
RL J. Bacteriol. 181:6469-6477(1999).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=11350964; DOI=10.1074/jbc.m101998200;
RA Tsai H.F., Fujii I., Watanabe A., Wheeler M.H., Chang Y.C., Yasuoka Y.,
RA Ebizuka Y., Kwon-Chung K.J.;
RT "Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-
RT length shortening of a heptaketide precursor.";
RL J. Biol. Chem. 276:29292-29298(2001).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF SER-257; ASP-352
RP AND HIS-380, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15310761; DOI=10.1074/jbc.m406758200;
RA Fujii I., Yasuoka Y., Tsai H.F., Chang Y.C., Kwon-Chung K.J., Ebizuka Y.;
RT "Hydrolytic polyketide shortening by ayg1p, a novel enzyme involved in
RT fungal melanin biosynthesis.";
RL J. Biol. Chem. 279:44613-44620(2004).
RN [5]
RP FUNCTION.
RX PubMed=19703288; DOI=10.1186/1471-2180-9-177;
RA Pihet M., Vandeputte P., Tronchin G., Renier G., Saulnier P.,
RA Georgeault S., Mallet R., Chabasse D., Symoens F., Bouchara J.P.;
RT "Melanin is an essential component for the integrity of the cell wall of
RT Aspergillus fumigatus conidia.";
RL BMC Microbiol. 9:177-177(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19156203; DOI=10.1371/journal.pone.0004224;
RA Jackson J.C., Higgins L.A., Lin X.;
RT "Conidiation color mutants of Aspergillus fumigatus are highly pathogenic
RT to the heterologous insect host Galleria mellonella.";
RL PLoS ONE 4:E4224-E4224(2009).
RN [7]
RP FUNCTION.
RX PubMed=20145078; DOI=10.1128/aac.01504-09;
RA Ben-Ami R., Lewis R.E., Leventakos K., Latge J.P., Kontoyiannis D.P.;
RT "Cutaneous model of invasive aspergillosis.";
RL Antimicrob. Agents Chemother. 54:1848-1854(2010).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21501368; DOI=10.1111/j.1462-5822.2011.01605.x;
RA Volling K., Thywissen A., Brakhage A.A., Saluz H.P.;
RT "Phagocytosis of melanized Aspergillus conidia by macrophages exerts
RT cytoprotective effects by sustained PI3K/Akt signalling.";
RL Cell. Microbiol. 13:1130-1148(2011).
RN [9]
RP FUNCTION.
RX PubMed=21747802; DOI=10.3389/fmicb.2011.00096;
RA Thywissen A., Heinekamp T., Dahse H.M., Schmaler-Ripcke J., Nietzsche S.,
RA Zipfel P.F., Brakhage A.A.;
RT "Conidial dihydroxynaphthalene melanin of the human pathogenic fungus
RT Aspergillus fumigatus interferes with the host endocytosis pathway.";
RL Front. Microbiol. 2:96-96(2011).
RN [10]
RP FUNCTION.
RX PubMed=21573171; DOI=10.1371/journal.pone.0019591;
RA Mech F., Thywissen A., Guthke R., Brakhage A.A., Figge M.T.;
RT "Automated image analysis of the host-pathogen interaction between
RT phagocytes and Aspergillus fumigatus.";
RL PLoS ONE 6:E19591-E19591(2011).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24818666; DOI=10.1128/iai.01726-14;
RA Bayry J., Beaussart A., Dufrene Y.F., Sharma M., Bansal K., Kniemeyer O.,
RA Aimanianda V., Brakhage A.A., Kaveri S.V., Kwon-Chung K.J., Latge J.P.,
RA Beauvais A.;
RT "Surface structure characterization of Aspergillus fumigatus conidia
RT mutated in the melanin synthesis pathway and their human cellular immune
RT response.";
RL Infect. Immun. 82:3141-3153(2014).
RN [12]
RP FUNCTION.
RX PubMed=25684622; DOI=10.1111/1462-2920.12808;
RA Hillmann F., Novohradska S., Mattern D.J., Forberger T., Heinekamp T.,
RA Westermann M., Winckler T., Brakhage A.A.;
RT "Virulence determinants of the human pathogenic fungus Aspergillus
RT fumigatus protect against soil amoeba predation.";
RL Environ. Microbiol. 17:2858-2869(2015).
RN [13]
RP SUBCELLULAR LOCATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26972005; DOI=10.1016/j.celrep.2016.02.059;
RA Upadhyay S., Xu X., Lowry D., Jackson J.C., Roberson R.W., Lin X.;
RT "Subcellular compartmentalization and trafficking of the biosynthetic
RT machinery for fungal melanin.";
RL Cell Rep. 14:2511-2518(2016).
CC -!- FUNCTION: Heptaketide hydrolyase; part of the gene cluster that
CC mediates the biosynthesis of dihydroxynaphthalene (DHN)-melanin, a
CC bluish-green pigment and a structural component of the conidial wall
CC (PubMed:10515939, PubMed:11350964, PubMed:15310761, PubMed:19156203).
CC The first step of the pathway is the production of the heptaketide
CC naphtopyrone YWA1 by the polyketide synthase alb1 though condensation
CC of acetyl-CoA with malonyl-CoA (PubMed:10515939). The naphtopyrone YWA1
CC is then converted to the pentaketide 1,3,6,8-tetrahydroxynaphthalene
CC (1,3,6,8-THN) by the heptaketide hydrolyase ayp1 though chain-length
CC shortening (PubMed:10515939, PubMed:11350964). 1,3,6,8-THN is substrate
CC of the hydroxynaphthalene reductase arp2 to yield scytalone
CC (PubMed:10515939, PubMed:11350964, PubMed:15310761). The scytalone
CC dehydratase arp1 then reduces scytalone to 1,3,8-THN (PubMed:10515939).
CC 1,3,8-THN is also substrate of the hydroxynaphthalene reductase arp2 to
CC yield vermelone (PubMed:10515939). Vermelone is further converted by
CC the multicopper oxidase abr1 to 1,8-DHN (PubMed:10515939). Finally the
CC laccase abr2 transforms 1,8-DHN to DHN-melanin (PubMed:10515939). DHN-
CC melanin biosynthesis appears to be initiated in endosomes where early
CC enzymes (abl1, ayg1, arp1 and arp2) localize, with exocytosis leading
CC to melanin deposition on the cell surface where late enzymes (abr1 and
CC abr2) localize (PubMed:26972005). DHN-melanin is an important
CC structural component of the outer cell wall and is required for the
CC presence of conidial surface hydrophobins (PubMed:19703288). DHN-
CC melanin also plays a crucial role in fungal virulence, including a
CC protective role against the host's immune defenses (PubMed:19156203,
CC PubMed:20145078, PubMed:21501368, PubMed:21747802, PubMed:21573171,
CC PubMed:24818666). DHN-melanin protects also conidia against amoeba
CC predation (PubMed:25684622). {ECO:0000269|PubMed:10515939,
CC ECO:0000269|PubMed:11350964, ECO:0000269|PubMed:15310761,
CC ECO:0000269|PubMed:19156203, ECO:0000269|PubMed:19703288,
CC ECO:0000269|PubMed:20145078, ECO:0000269|PubMed:21501368,
CC ECO:0000269|PubMed:21573171, ECO:0000269|PubMed:21747802,
CC ECO:0000269|PubMed:24818666, ECO:0000269|PubMed:25684622,
CC ECO:0000269|PubMed:26972005}.
CC -!- ACTIVITY REGULATION: Serine protease inhibitors strongly inhibit
CC activity (PubMed:15310761). Moreover, 3,4-dichloroisocoumarinshows and
CC 2-acetyl-1,3,6,8-tetrahydroxynaphthalene act also as a strong inhibitor
CC (PubMed:15310761). {ECO:0000269|PubMed:15310761}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=44 uM for naphtopyrone YWA1 {ECO:0000269|PubMed:15310761};
CC -!- PATHWAY: Pigment biosynthesis; melanin biosynthesis.
CC {ECO:0000269|PubMed:10515939}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q93NG6}.
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000269|PubMed:26972005}.
CC -!- DISRUPTION PHENOTYPE: Leads to a yellow-green color of conidia
CC (PubMed:11350964, PubMed:26972005). Impairs the accumulation of
CC 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) (PubMed:11350964).
CC Results in an altered conidial surface with masked surface rodlet
CC layer, leaky cell wall allowing the deposition of proteins on the cell
CC surface and exposing the otherwise-masked cell wall polysaccharides at
CC the surface (PubMed:24818666). Decreases the protection against the
CC host's immune defenses (PubMed:21501368). Causes enhanced insect
CC mortality compared to the parent strain in a wax moth Galleria
CC mellonella infection model, probably through exacerbated immune
CC response of the wax moth (PubMed:19156203).
CC {ECO:0000269|PubMed:11350964, ECO:0000269|PubMed:19156203,
CC ECO:0000269|PubMed:21501368, ECO:0000269|PubMed:24818666,
CC ECO:0000269|PubMed:26972005}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94052.1; -; Genomic_DNA.
DR RefSeq; XP_756090.1; XM_750997.1.
DR AlphaFoldDB; Q4WZB3; -.
DR SMR; Q4WZB3; -.
DR STRING; 746128.CADAFUBP00003258; -.
DR ESTHER; aspfu-AYG1; Duf_1100-S.
DR EnsemblFungi; EAL94052; EAL94052; AFUA_2G17550.
DR GeneID; 3513286; -.
DR KEGG; afm:AFUA_2G17550; -.
DR VEuPathDB; FungiDB:Afu2g17550; -.
DR eggNOG; ENOG502S29V; Eukaryota.
DR HOGENOM; CLU_053723_1_0_1; -.
DR InParanoid; Q4WZB3; -.
DR OMA; WILGDKF; -.
DR OrthoDB; 599073at2759; -.
DR UniPathway; UPA00785; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0042438; P:melanin biosynthetic process; IMP:AspGD.
DR GO; GO:0046148; P:pigment biosynthetic process; IMP:AspGD.
DR GO; GO:0030640; P:polyketide catabolic process; IMP:AspGD.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR010520; FrsA-like.
DR Pfam; PF06500; FrsA-like; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Endosome; Hydrolase; Reference proteome.
FT CHAIN 1..406
FT /note="Heptaketide hydrolyase ayg1"
FT /id="PRO_0000436878"
FT ACT_SITE 257
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:15310761"
FT ACT_SITE 352
FT /evidence="ECO:0000269|PubMed:15310761"
FT ACT_SITE 380
FT /evidence="ECO:0000269|PubMed:15310761"
FT MUTAGEN 257
FT /note="S->A: Results in a complete loss of enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:15310761"
FT MUTAGEN 352
FT /note="D->A: Results in a complete loss of enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:15310761"
FT MUTAGEN 380
FT /note="H->A: Results in a complete loss of enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:15310761"
SQ SEQUENCE 406 AA; 45217 MW; CA19A32372DC5B5B CRC64;
MPRWILGDKF DTVFPHKGSL KVLWESRWKS ACSKSVYPFH DGSIEDFEPI FNHLISKNIN
DAASDEYTQA FLPTASALEE KAAQALQAGK HEEASNLLCR AAVVYRISRF PYVDITKPSS
IKRVAFERQK QAYLKATSLW TQPIREVTVP HTYRTGNDGA HIPIYIRTPA GADQSNPVPI
VLIMTGLDGY RSDNSQRTHE ILARGWAAVV AEIPGTADCP ADPADPASPD RLWDSVLSYL
DQRPELNTAK MVVWGLSAGG YYAIRAAHTH RDRLLGAIAH GPGCHYYLDP EWLAKVNDHE
YPFEITAAWA TKHGYKTVEE FVAGAQKKFS LVETGIVDQP SCRLLLLNGV DDGVVPIEDC
LVLFEHGSPK EGRFYKGLPH MGYPNSLPVS YEWLEQVLAS PSKTKN
