CSYB_ASPOR
ID CSYB_ASPOR Reviewed; 397 AA.
AC Q2U852; Q53U84;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Acylalkylpyrone synthase csyB {ECO:0000303|PubMed:25564614};
DE EC=2.3.1.- {ECO:0000269|PubMed:20471846, ECO:0000269|PubMed:23290452, ECO:0000269|PubMed:24011646, ECO:0000269|PubMed:24895122, ECO:0000269|PubMed:25564614};
DE AltName: Full=Type III polyketide synthase csyB {ECO:0000303|PubMed:15845386};
GN Name=csyB {ECO:0000303|PubMed:15845386}; ORFNames=AO090701000566;
OS Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=510516;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, AND INDUCTION.
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=15845386; DOI=10.1016/j.bbrc.2005.03.160;
RA Seshime Y., Juvvadi P.R., Fujii I., Kitamoto K.;
RT "Discovery of a novel superfamily of type III polyketide synthases in
RT Aspergillus oryzae.";
RL Biochem. Biophys. Res. Commun. 331:253-260(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=16372010; DOI=10.1038/nature04300;
RA Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA Kikuchi H.;
RT "Genome sequencing and analysis of Aspergillus oryzae.";
RL Nature 438:1157-1161(2005).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20471846; DOI=10.1016/j.bmc.2010.04.058;
RA Seshime Y., Juvvadi P.R., Kitamoto K., Ebizuka Y., Fujii I.;
RT "Identification of csypyrone B1 as the novel product of Aspergillus oryzae
RT type III polyketide synthase CsyB.";
RL Bioorg. Med. Chem. 18:4542-4546(2010).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23290452; DOI=10.1016/j.bmcl.2012.11.119;
RA Hashimoto M., Seshime Y., Kitamoto K., Uchiyama N., Goda Y., Fujii I.;
RT "Identification of csypyrone B2 and B3 as the minor products of Aspergillus
RT oryzae type III polyketide synthase CsyB.";
RL Bioorg. Med. Chem. Lett. 23:650-653(2013).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24011646; DOI=10.1016/j.bmcl.2013.08.036;
RA Hashimoto M., Ishida S., Seshime Y., Kitamoto K., Fujii I.;
RT "Aspergillus oryzae type III polyketide synthase CsyB uses a fatty acyl
RT starter for the biosynthesis of csypyrone B compounds.";
RL Bioorg. Med. Chem. Lett. 23:5637-5640(2013).
RN [6]
RP CRYSTALLIZATION, AND FUNCTION.
RX PubMed=24915080; DOI=10.1107/s2053230x14008516;
RA Yang D., Mori T., Matsui T., Hashimoto M., Morita H., Fujii I., Abe I.;
RT "Expression, purification and crystallization of a fungal type III
RT polyketide synthase that produces the csypyrones.";
RL Acta Crystallogr. F Struct. Biol. Commun. 70:730-733(2014).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=24895122; DOI=10.1074/jbc.m114.569095;
RA Hashimoto M., Koen T., Takahashi H., Suda C., Kitamoto K., Fujii I.;
RT "Aspergillus oryzae CsyB catalyzes the condensation of two beta-ketoacyl-
RT CoAs to form 3-acetyl-4-hydroxy-6-alkyl-alpha-pyrone.";
RL J. Biol. Chem. 289:19976-19984(2014).
RN [8] {ECO:0007744|PDB:3WXY, ECO:0007744|PDB:3WXZ, ECO:0007744|PDB:3WY0}
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEX WITH COENZYME A, SUBUNIT,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ALA-265; ILE-375 AND
RP HIS-377.
RX PubMed=25564614; DOI=10.1074/jbc.m114.626416;
RA Mori T., Yang D., Matsui T., Hashimoto M., Morita H., Fujii I., Abe I.;
RT "Structural basis for the formation of acylalkylpyrones from two beta-
RT ketoacyl units by the fungal type III polyketide synthase CsyB.";
RL J. Biol. Chem. 290:5214-5225(2015).
CC -!- FUNCTION: Acylalkylpyrone synthase that catalyzes not only the
CC polyketide chain elongation but also the one-pot condensation of two
CC beta-ketoacyl units to produce the 3-acyl-4-hydroxy-6-alkyl-alpha-
CC pyrone (AcAP) scaffold, a precursor of csypyrone B (PubMed:20471846,
CC PubMed:23290452, PubMed:24011646, PubMed:24895122, PubMed:25564614)
CC (Probable). The enzyme reaction is initiated by the loading of
CC acetoacetyl-CoA onto Cys-155, and subsequent thioester bond cleavage by
CC the nucleophilic water generates the beta-keto acid intermediate, which
CC is placed within a pocket (PubMed:25564614). The second beta-ketoacyl
CC unit is then produced by polyketide chain elongation of fatty acyl-CoA
CC with one molecule of malonyl-CoA, and the condensation with the beta-
CC ketoacid generates the final products (PubMed:24895122,
CC PubMed:25564614). Csypyrone B1 is the major product and contains a
CC propanoic acid side-chain, whereas csypyrones B2 and B3 are minor
CC compounds that contain butyric or pentanoic acid side-chains,
CC respectively (PubMed:20471846, PubMed:23290452, PubMed:24011646).
CC {ECO:0000269|PubMed:20471846, ECO:0000269|PubMed:23290452,
CC ECO:0000269|PubMed:24011646, ECO:0000269|PubMed:24895122,
CC ECO:0000269|PubMed:25564614, ECO:0000305|PubMed:24915080}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.4 uM for acetoacetyl-CoA {ECO:0000269|PubMed:24895122};
CC KM=6.4 mM for C(4)-diketide-N-acetylcysteamine
CC {ECO:0000269|PubMed:25564614};
CC KM=3.1 mM for C(5)-diketide-N-acetylcysteamine
CC {ECO:0000269|PubMed:25564614};
CC KM=6.8 mM for C(6)-diketide-N-acetylcysteamine
CC {ECO:0000269|PubMed:25564614};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25564614}.
CC -!- INDUCTION: Expressed during 1-3 days of culture in DPY medium.
CC {ECO:0000269|PubMed:15845386}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene
CC synthases family. {ECO:0000305}.
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DR EMBL; AB206759; BAD97391.1; -; Genomic_DNA.
DR EMBL; AP007164; BAE62263.1; -; Genomic_DNA.
DR PDB; 3WXY; X-ray; 1.71 A; A/B=1-397.
DR PDB; 3WXZ; X-ray; 2.30 A; A/B=1-397.
DR PDB; 3WY0; X-ray; 2.00 A; A/B=1-397.
DR PDBsum; 3WXY; -.
DR PDBsum; 3WXZ; -.
DR PDBsum; 3WY0; -.
DR AlphaFoldDB; Q2U852; -.
DR SMR; Q2U852; -.
DR EnsemblFungi; BAE62263; BAE62263; AO090701000566.
DR VEuPathDB; FungiDB:AO090701000566; -.
DR HOGENOM; CLU_034992_1_1_1; -.
DR OMA; NFMGCYA; -.
DR Proteomes; UP000006564; Chromosome 5.
DR GO; GO:0034083; C:type III polyketide synthase complex; IDA:AspGD.
DR GO; GO:0016210; F:naringenin-chalcone synthase activity; ISA:AspGD.
DR GO; GO:0090439; F:tetraketide alpha-pyrone synthase activity; IDA:AspGD.
DR GO; GO:0030639; P:polyketide biosynthetic process; IDA:AspGD.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR012328; Chalcone/stilbene_synt_C.
DR InterPro; IPR001099; Chalcone/stilbene_synt_N.
DR InterPro; IPR011141; Polyketide_synthase_type-III.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR11877; PTHR11877; 1.
DR Pfam; PF02797; Chal_sti_synt_C; 1.
DR Pfam; PF00195; Chal_sti_synt_N; 1.
DR PIRSF; PIRSF000451; PKS_III; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Reference proteome; Transferase.
FT CHAIN 1..397
FT /note="Acylalkylpyrone synthase csyB"
FT /id="PRO_0000452729"
FT ACT_SITE 155
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10023,
FT ECO:0000269|PubMed:25564614"
FT ACT_SITE 377
FT /evidence="ECO:0000269|PubMed:25564614"
FT BINDING 50..57
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P30074"
FT BINDING 50
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:25564614,
FT ECO:0007744|PDB:3WXY"
FT BINDING 214..215
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P30074"
FT BINDING 267
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:25564614,
FT ECO:0007744|PDB:3WXY"
FT BINDING 312..315
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q58VP7"
FT BINDING 312
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:25564614,
FT ECO:0007744|PDB:3WXY"
FT BINDING 314
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:25564614,
FT ECO:0007744|PDB:3WXY"
FT BINDING 315
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:25564614,
FT ECO:0007744|PDB:3WXY"
FT MUTAGEN 265
FT /note="A->F,V: Leads to almost complete loss of catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:25564614"
FT MUTAGEN 375
FT /note="I->F: Does not affect the catalytic activity."
FT /evidence="ECO:0000269|PubMed:25564614"
FT MUTAGEN 375
FT /note="I->W: Leads to complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:25564614"
FT MUTAGEN 377
FT /note="H->F,P: Leads to complete loss of catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:25564614"
FT STRAND 15..24
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 31..41
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 46..55
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 82..108
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 157..175
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 193..203
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 209..212
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 216..223
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 236..246
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 271..288
FT /evidence="ECO:0007829|PDB:3WXY"
FT TURN 291..295
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 314..323
FT /evidence="ECO:0007829|PDB:3WXY"
FT TURN 328..331
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 332..339
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:3WXY"
FT HELIX 348..361
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 368..376
FT /evidence="ECO:0007829|PDB:3WXY"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:3WXY"
FT STRAND 380..387
FT /evidence="ECO:0007829|PDB:3WXY"
SQ SEQUENCE 397 AA; 43079 MW; 2071EAF7D3492D11 CRC64;
MIEPLPTEDI PKQSVSIVGI ASRCAPHKLG ADELEAIARR HYSSTPSLEK MLEINRKTRI
DHRYSVFSSD HEHWHRPTIP SFSECDSLFK EYGIPLASAA SARAIQDWGG VPDEITHLVA
VTCTNTAHPG FDSVLCRKLG LKCNVRRVLL HGIGCGGGIS AMRVAHELLL GSTQQGVPAR
ALIVACEVPT VFARSELDIM DKTQDVNVAM CLFGDCAAAL VLSNGIGHKA SEQRPIWNIL
NCEPTQFDGT EDIAHFNVHD KGYHAIIDKR IPQLTGKCVP AGFQSLISST PSLALEEKNY
VPSNYGWAVH PGGYAVLVAA QDALGLTADD LRASYDAYRD GGNTISTTII RILEKLRDEH
KHGSNQKDKL VLAAIGHGIT LETAILTRPG SSSYLHA
