ASTA_ASPOR
ID ASTA_ASPOR Reviewed; 1338 AA.
AC Q2UEK2;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 25-MAY-2022, entry version 93.
DE RecName: Full=Nonribosomal peptide synthetase astA {ECO:0000303|PubMed:27628599};
DE EC=6.3.2.- {ECO:0000269|PubMed:27628599};
DE AltName: Full=Astellolide biosynthesis cluster protein A {ECO:0000303|PubMed:27628599};
GN Name=astA {ECO:0000303|PubMed:27628599}; ORFNames=AO090026000585;
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 [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 [2]
RP INDUCTION, FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=27628599; DOI=10.1038/srep32865;
RA Shinohara Y., Takahashi S., Osada H., Koyama Y.;
RT "Identification of a novel sesquiterpene biosynthetic machinery involved in
RT astellolide biosynthesis.";
RL Sci. Rep. 6:32865-32865(2016).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of astellolides, drimane-type
CC sesquiterpene esters that show antimicrobial, anti-inflammatory, and
CC anti-tumor activities (PubMed:27628599). The first step in astellolide
CC biosynthesis is performed by the sesquiterpene cyclase astC that
CC catalyzes the formation of drimanyl pyrophosphate from farnesyl
CC pyrophosphate (PubMed:27628599). Drimanyl pyrophosphate is then
CC dephosphorylated by the sesquiterpene phosphatase astI to produce
CC drimanyl monophosphate which is further dephosphorylated to drim-8-ene-
CC 11-ol by atsK (PubMed:27628599). Drim-8-ene-11-ol is converted to
CC confertifolin, probably by the cytochrome P450 monooxygenase astD
CC and/or the dehydrogenase astE (PubMed:27628599). The cytochrome P450
CC monooxygenases astB, astF and astJ then hydroxylate confertifolin at
CC C6, C14, or C15 to form trihydroxy confertifolin (PubMed:27628599). The
CC nonribosomal peptide synthetase astA catalyzes ester bond formation
CC between trihydroxy contifolin and benzoic acid (BA) or 4-hydroxy
CC benzoic acid (4HBA), leading to the formation of dideacetyl
CC astellolides A and B, respectively (PubMed:27628599). Finally, the O-
CC acetyltransferase astG converts dideacetyl astellolides A and B into
CC deacetyl astellolides A and B (PubMed:27628599).
CC {ECO:0000269|PubMed:27628599}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27628599}.
CC -!- INDUCTION: Expression is regulated by the secondary metabolite
CC regulator cclA. {ECO:0000269|PubMed:27628599}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. AsrA has the following single
CC module architecture: A-T-C. {ECO:0000305|PubMed:27628599}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of deacetyl astellolides A
CC and B and leads to the accumulation of trihydroxy confertifolin.
CC {ECO:0000269|PubMed:27628599}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; AP007159; BAE60013.1; -; Genomic_DNA.
DR RefSeq; XP_001822015.1; XM_001821963.1.
DR AlphaFoldDB; Q2UEK2; -.
DR SMR; Q2UEK2; -.
DR EnsemblFungi; BAE60013; BAE60013; AO090026000585.
DR GeneID; 5994043; -.
DR KEGG; aor:AO090026000585; -.
DR VEuPathDB; FungiDB:AO090026000585; -.
DR HOGENOM; CLU_000022_60_3_1; -.
DR OMA; HANAWIV; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000006564; Chromosome 3.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR009081; PP-bd_ACP.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome.
FT CHAIN 1..1338
FT /note="Nonribosomal peptide synthetase astA"
FT /id="PRO_0000450113"
FT DOMAIN 820..893
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 22..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..681
FT /note="Adenylation"
FT /evidence="ECO:0000255"
FT REGION 949..1336
FT /note="Condensation"
FT /evidence="ECO:0000255"
FT COMPBIAS 33..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 854
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1338 AA; 146209 MW; 754217529968493D CRC64;
MDLEPWGPLY RKQDQDGSLD NIAVVSGDIP SPHPKNEPSQ TSTLHIPRDS DLDSDIPSVP
TALIIAWGLT LSSLTGDEVV GFDLLPFRGD YQDLGARPYH FLLKFGYREW SREAATTGMD
LGSASSEGLP QGMGNRPQIA PSRFRNVLII KQCSDAPGDS GSLESPSLGN VDKDEPTDAF
RADMFISIQC GIGRTGIDVH CSFDPAFWTS ENIRMILLDL SRNFKEVMRC GRDDTPLTCL
EGMSPKGLDC VLRRNIIPPP PKMEACVHHR FQARCRQNPS ALAIDAWDGQ LTYAELDSLS
SQLASRLVSS ITICPRGFMG VLMEKSAWVP VAILAVLKVG SAFVFLDGSQ PLQRLKIICA
ETKSQLVLSS AHYREKANTL GPPVLLVEKN QSGLGQAKEN DSCPSLLEDY PQPQSQPQDT
LYAVFTSGST GEPKGAMVDH GAFCTMCGPQ MAARPTTNVS PRVFQFAPHA FTVSILDYLG
TLLQGGCVCV PSEEELRNNM AGAIEGLSAN IVTMTPSMAR VLDPTQTPSL QLVLLAGEMM
AQCDLDKWSQ CVRLLSLYGQ SENAAGSMIS EKSIVPRAPN TFETLTPGFQ CWIVSQDNPH
RLMALGEVGE LLLEGPALGQ GYMNDPIQTE DKFICRSFCL EYAHSGSPQS YRLFKTGDLV
RYTPAGEIEL LGRKGAEVKL RGQRIDLTEI EHHLRCLFPS ATRVVADVII PSDDIDGLHP
VLAAFVQVDS VSRTGQSAEA TFASPRPEFR AEAKAVLSGL CQTIPSYMIP MTIIPTEAFP
FTATGKLDRR SLRQYASAMS RSDLLKYVTD DRGPVVTAVT PVEIIIHDAC VEALGVSSDK
VGMLDSFPDL GGDSLAARRM VSICRTKGLE LAVADILAHS SLTSLAEKCS AGGGGAKQIS
QGVEMLDPFS TAKEEFLSHL PSFLPNADMI ADVFPVQGAQ RRAARAIDTF IFRLSGPVDA
DRLRDACQVL QQAHLALRSI FVPFYGKFMQ VVLRVPPLDF TRRLLPDGTD LVKWAESIGQ
ADKTQRPPSE EFVVRFTLAE TAGTPDYSIF MMRLSHAQYD AGCLARIISD LWAVYEQKQL
VVKSDFAQYA RRAVQQTHLL SMEAFWRDLL AGTTGLTPLP VTGISAEEER TIIVQQRVEL
KEPPPTGISM ATVVRGAWSW VLHQQTGNTV VVFNEMLNGR DVVPLEDTEP VVGACHSIVP
VCVHFPLPQS GRTPRELLSA LQEQHLASLT FTTLDRDYLI QNCTEWTSHQ SGFILAYQNF
PEICDLVIGE DLSCQWASQV LDLAEPGEAW VTATPLPGAL QISLRVSTAA MDEQEANAWI
SALGQTIIRF LDSPDSVL
