BTYA_ASPTN
ID BTYA_ASPTN Reviewed; 930 AA.
AC Q0CU19; A0A2I6SS16;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Nonribosomal peptide synthetase btyA {ECO:0000303|PubMed:23841722};
DE EC=2.3.1.- {ECO:0000269|PubMed:29305695};
DE AltName: Full=Butyrolactone IIa synthetase {ECO:0000303|PubMed:23841722};
GN Name=btyA {ECO:0000303|PubMed:29305695}; ORFNames=ATEG_02815;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=NIH 2624 / FGSC A1156;
RX PubMed=29305695; DOI=10.1007/s00253-017-8719-1;
RA Huehner E., Backhaus K., Kraut R., Li S.M.;
RT "Production of alpha-keto carboxylic acid dimers in yeast by overexpression
RT of NRPS-like genes from Aspergillus terreus.";
RL Appl. Microbiol. Biotechnol. 102:1663-1672(2018).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION, DOMAIN, FUNCTION, AND PATHWAY.
RX PubMed=23841722; DOI=10.1021/ol401384v;
RA Guo C.J., Knox B.P., Sanchez J.F., Chiang Y.M., Bruno K.S., Wang C.C.;
RT "Application of an efficient gene targeting system linking secondary
RT metabolites to their biosynthetic genes in Aspergillus terreus.";
RL Org. Lett. 15:3562-3565(2013).
RN [4]
RP DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=27978657; DOI=10.1021/acs.orglett.6b02821;
RA van Dijk J.W., Guo C.J., Wang C.C.;
RT "Engineering fungal nonribosomal peptide synthetase-like enzymes by
RT heterologous expression and domain swapping.";
RL Org. Lett. 18:6236-6239(2016).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of butyrolactones, natural products that
CC show a wide range of biological activities such as antitumor,
CC antiparasitic or anti-inflammatory activity (PubMed:29305695,
CC PubMed:23841722, PubMed:27978657). The nonribosomal peptide synthetase
CC btyA is responsible for the production of butyrolactone II, the core
CC structure of butyrolactones (PubMed:29305695, PubMed:27978657). BtyA
CC first activates 4-hydroxyphenylpyruvate (HPPA) through its A domain to
CC AMP-HPPA (Probable). The HPPA unit is then loaded to the T domain and
CC eventually transferred to the TE domain (Probable). Upon loading of
CC another HPPA unit to the T domain, the TE domain promotes the enolate
CC formation on the unit attached (Probable). Then aldol condensation
CC establishes the carbon-carbon bond between the two units, followed by
CC ester cyclization, and keto-enol tautomerization to yield the gamma-
CC butyrolactone core (Probable). Hydrolysis, and finally esterification
CC of the exposed carboxylic acid group yields butyrolactone II
CC (Probable). Two additional enzymes, a prenyltransferase and an
CC epoxidase, may be involved in the tailoring modifications of
CC butyrolactone II to give butyrolactone III and butyrolactone I
CC (Probable). {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:27978657,
CC ECO:0000269|PubMed:29305695, ECO:0000305|PubMed:23841722,
CC ECO:0000305|PubMed:27978657}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 3-(4-hydroxyphenyl)pyruvate + H(+) = (2S)-2-(4-
CC hydoxybenzyl)-3-(4-hydroxyphenyl)-2-furonol carboxylate + H2O;
CC Xref=Rhea:RHEA:63900, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:36242, ChEBI:CHEBI:149630;
CC Evidence={ECO:0000269|PubMed:29305695};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63901;
CC Evidence={ECO:0000269|PubMed:29305695};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:27978657,
CC ECO:0000269|PubMed:29305695}.
CC -!- DOMAIN: BtyA has an A-T-TE domain architecture (Probable). The
CC adenylation (A) domain recognizes and activates the aryl acid
CC substrates, and loads them onto the thiolation (T) domain (Probable).
CC The thioesterase (TE) domain shares the missing condensation (C) domain
CC function, and is responsible for condensation and final product release
CC (Probable). {ECO:0000305|PubMed:23841722, ECO:0000305|PubMed:27978657,
CC ECO:0000305|PubMed:29305695}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAU36089.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; MG384314; AUO29224.1; -; mRNA.
DR EMBL; CH476597; EAU36089.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001211993.1; XM_001211993.1.
DR AlphaFoldDB; Q0CU19; -.
DR SMR; Q0CU19; -.
DR STRING; 33178.CADATEAP00010015; -.
DR EnsemblFungi; EAU36089; EAU36089; ATEG_02815.
DR GeneID; 4317761; -.
DR eggNOG; KOG1176; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_23_6_1; -.
DR OrthoDB; 1565999at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..930
FT /note="Nonribosomal peptide synthetase btyA"
FT /id="PRO_0000450544"
FT DOMAIN 570..647
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:23841722, ECO:0000305|PubMed:27978657,
FT ECO:0000305|PubMed:29305695"
FT REGION 31..440
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23841722,
FT ECO:0000305|PubMed:27978657, ECO:0000305|PubMed:29305695"
FT REGION 667..920
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23841722,
FT ECO:0000305|PubMed:27978657, ECO:0000305|PubMed:29305695"
FT MOD_RES 607
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 930 AA; 102579 MW; A15200800DDFAEB4 CRC64;
MTKIDLINLL DHAADTVAAS GILIYSPGNV ESPHRLTYAE LRDAAQQNAR RLGCMEGFAP
GSLVLLHLDG YRDNMIWLWS LIYAGCIPVM STPFAHHEEH RRSHLLHLQS LLRDPICLTR
QGLEAQFPPD VGFRLCNIES ISGGSNPFTS PRLGQPPGQD DNVDDIALLM LTSGSTGHAK
AVPLTHSQLL SALAGKERFL QLRQHGPSLN WVAFDHIASL AEMHFHPIFA CIDQVHVAAA
DVITDPLILL ELIHRHRVGI TFAPNFLLAK LLDSLEREPS PSSRPWDLSC LMHLLSGGEA
NVVDTCARLA RRLTQDYGVP STCIKPAFGM TETCAGCSFN DRFPTYETVH MLDFASLGRG
VKGVQMRVTS LSTGQPVDDH SEVGNLELSG PSVFRGYYNN SQATRDSFTP DGWFRTGDLA
MIDAGGQLVL RGRSKELICI NGAKYLPHEV ESAIEDAKVR GVTPGFTICF GYRPAKAQTE
SLAVVYLPAY EEADVESRSQ AQNAIIRVGL IMTGTRPYVL PLDAHTLVKS SLGKISRNKI
KTGLESGAFQ AFEETNNRLL KLRQSTPVVP AGNETETLLL AAALHVFRVT ADEFGVETPM
FAFGITSLDM IAWKRQAETI LGHEIPMLAI ITSPTIRVLA RQLQDGHHGP GEYNPVVTLQ
PHGSKTPLWL IHPIGGEVLV FVSLAGLFAD DRPVHALRAR GLNRGEPPFG SIHEAADAYY
QAIKRVQPHG PYAVAGYSYG SLVAFEVAKR LDQHGKDEVP FFGSLDLPPF HAQIISKSDW
TESLLHLASS LSLIAEEEIN TLGADLRGLP QPRAIQKILA RAPPRRIREL DLSPDGLMRW
TKLTSAMAQA TRGYVPVGQT RSVDVFYTEP SGALATTRDE WLDRHREWRQ FGRLETQFHP
LEGLHYRLMD EDNVHKVYRV LSRAMDARGL
