ID   ASAC_ASPFN              Reviewed;        1021 AA.
AC   B8N0E8;
DT   20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 79.
DE   RecName: Full=Nonribosomal peptide synthetase asaC {ECO:0000303|PubMed:29674152};
DE            Short=NRPS asaC {ECO:0000303|PubMed:29674152};
DE            EC=6.3.2.- {ECO:0000269|PubMed:29674152};
DE   AltName: Full=Aspergillic acid biosynthesis cluster protein C {ECO:0000303|PubMed:29674152};
GN   Name=asaC {ECO:0000303|PubMed:29674152}; ORFNames=AFLA_023020;
OS   Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS   / JCM 12722 / SRRC 167).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=332952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC   167;
RX   PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA   Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA   Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT   "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT   aflatoxin contamination of food and feed.";
RL   Genome Announc. 3:E0016815-E0016815(2015).
RN   [2]
RP   IDENTIFICATION WITHIN THE CLUSTER, AND INDUCTION.
RX   PubMed=23834374; DOI=10.1111/mpp.12056;
RA   Dolezal A.L., Obrian G.R., Nielsen D.M., Woloshuk C.P., Boston R.S.,
RA   Payne G.A.;
RT   "Localization, morphology and transcriptional profile of Aspergillus flavus
RT   during seed colonization.";
RL   Mol. Plant Pathol. 14:898-909(2013).
RN   [3]
RP   FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=29674152; DOI=10.1016/j.fgb.2018.04.009;
RA   Lebar M.D., Cary J.W., Majumdar R., Carter-Wientjes C.H., Mack B.M.,
RA   Wei Q., Uka V., De Saeger S., Diana Di Mavungu J.;
RT   "Identification and functional analysis of the aspergillic acid gene
RT   cluster in Aspergillus flavus.";
RL   Fungal Genet. Biol. 116:14-23(2018).
CC   -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC       that mediates the biosynthesis of aspergillic acid, a hydroxamic acid-
CC       containing pyrazinone with aliphatic side chains that originates from
CC       leucine (Leu) and isoleucine (Ile) (PubMed:29674152). Aspergillic acid
CC       has antibiotic properties and was shown to be lethal to mice
CC       (PubMed:29674152). The first step in the pathway is the production of
CC       deoxyaspergillic acid via a condensation between the Ile amine and the
CC       Leu carboxylic acid, followed by a reductive release from the protein
CC       forming the dipeptide aldehyde NH(2)-Leu-Ile-CHO, which could undergo
CC       an intermolecular cyclization resulting in a dihydropyrazinone
CC       (PubMed:29674152). As the NRPS asaC lacks a condensation domain, it is
CC       improbable that it is responsible for condensation of Leu and Ile
CC       (PubMed:29674152). One possibility is that asaC acts on a previously
CC       condensed dipeptide and functions as a Leu-Ile reductase to yield
CC       deoxyaspergillic acid (PubMed:29674152). After asaC forms
CC       deoxyaspergillic acid, the cytochrome P450 asaD oxidizes the pyrazinone
CC       to the hydroxamic acid-containing bioactive metabolite aspergillic acid
CC       (PubMed:29674152). The hydroxylase/desaturase asaB can then convert
CC       aspergillic acid to hydroxyaspergillic acid (PubMed:29674152). Both
CC       aspergillic acid and hydroxyaspergillic acid can form complexes with
CC       iron producing ferriaspergillin analogs (PubMed:29674152).
CC       {ECO:0000269|PubMed:29674152}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:29674152}.
CC   -!- INDUCTION: Expressed during the earliest stages of maize kernel
CC       infection (PubMed:23834374). {ECO:0000269|PubMed:23834374}.
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 (By similarity). Each module is responsible for the recognition
CC       (via the A domain) and incorporation of a single amino acid into the
CC       growing peptide product (By similarity). Thus, an NRP synthetase is
CC       generally composed of one or more modules and can terminate in a
CC       thioesterase domain (TE) that releases the newly synthesized peptide
CC       from the enzyme (By similarity). Occasionally, epimerase (E) domains
CC       (responsible for L- to D-amino acid conversion) are present within the
CC       NRP synthetase (By similarity). AsaC contains an amino acid adenylation
CC       domain (A), a peptidyl carrier protein (PCP) domain with a
CC       phosphopantetheine prosthetic group, and a short-chain
CC       dehydrogenase/reductase terminus (R), but it does not have an
CC       identifiable condensation (C) domain required for the formation of
CC       peptide bonds during non-ribosomal peptide synthesis (PubMed:29674152).
CC       {ECO:0000250|UniProtKB:Q4WAZ9, ECO:0000305|PubMed:29674152}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of ferriaspergillin and
CC       aspergillic acid (PubMed:29674152). {ECO:0000269|PubMed:29674152}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; EQ963473; EED55031.1; -; Genomic_DNA.
DR   RefSeq; XP_002373813.1; XM_002373772.1.
DR   AlphaFoldDB; B8N0E8; -.
DR   SMR; B8N0E8; -.
DR   STRING; 5059.CADAFLAP00001678; -.
DR   EnsemblFungi; EED55031; EED55031; AFLA_023020.
DR   VEuPathDB; FungiDB:AFLA_023020; -.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_2_17_1; -.
DR   OMA; HRTHILH; -.
DR   Proteomes; UP000001875; Unassembled WGS sequence.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR   CDD; cd05235; SDR_e1; 1.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.30.300.30; -; 1.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR025110; AMP-bd_C.
DR   InterPro; IPR045851; AMP-bd_C_sf.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR013120; Far_NAD-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   InterPro; IPR010080; Thioester_reductase-like_dom.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 1.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   2: Evidence at transcript level;
KW   Ligase; Multifunctional enzyme; Oxidoreductase; Phosphopantetheine;
KW   Phosphoprotein.
FT   CHAIN           1..1021
FT                   /note="Nonribosomal peptide synthetase asaC"
FT                   /id="PRO_0000444455"
FT   DOMAIN          528..603
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:29674152"
FT   REGION          17..418
FT                   /note="Adenylation (A) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:29674152"
FT   REGION          646..888
FT                   /note="short-chain dehydrogenase/reductase (R) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:29674152"
FT   MOD_RES         563
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1021 AA;  113315 MW;  B55B484101FD24C7 CRC64;
     MSIFSSISSL GLEACYRHHV RTSPNATAVV DGDQSMTYRE LETRVNDLAS ILGRENIEEE
     EPIGILVPMG IAHVVAQAAV LRLGGSCVPM DLSFPDQRIN DLLRALKTRI VLTVESEKAR
     FAEFQTILVD SKYANLHQNG YHEDTIPAVE TGRNHRTHIL HTSGTTGLPK PVEIMSKGIT
     RMAFNTQCVE FKSTDRVAQI SAPSFDAALF EIWTTLARGA AIVLLPKNVV IDPVALHDSL
     RKYRITSILV TTALLNHVVS AIPNAFEDLD YVLTGGEAAN PSVMQVILEN GPPKKLVHAY
     GPTECTIITT YHLTTLEEVR RGQTPIGRPL DNTTVYILDD NLQPVKEGIV GELYIGGDAV
     ARGYLGRPEA NAKSFLEVSH LSKDGSPVRI YRSGDLVRML DTGAIEFVAR ADNMVKIRGF
     RIEPAEIEGA LLKSEMVQGT VVLPVHRPGK ETYIVAFVIP KHDGAFSLEQ LDEYLRRRLP
     AYMMPRLEAV ASLPLTVHGK IDRVAVMKKH MEETKRAEQQ VLISSNVKDA GDSVTWLRTL
     WTSVLGISNI DNEASFFHLG GSSLQAAALL VHIRRRFGLT LTMQQIYDSP TLLGLASVID
     AGHAKSKVDH SRLGIFIADS QLAKDIPVLS KEAPDWRSPS EGKVFLTGAT GFLGTYFLRE
     LIDRPDVRSV KCLVRASDAH SARKRLLGAL DKYGLGWADN LDKVTAIAGD LGKDLFGLSE
     TEFHELALWT SVIFHVGAHV NYVQPYEKHR NTNVYGTLNC IKLATTGRTK ALHYTSTAAV
     TGPVSHFTGA DKIPEDVDLG EFQGWLPYDI GYTQSKWVSE QLIHSMIAKG LPAIVFRPGF
     IMGDSLRGKG NCDDFMCRVF IGSIKLGYRP ILPNQSKIMI PVDFITTALL HITSNPYNFG
     RTFHLVPQTP EEDTDIETSW NMLKELGYDL KAVEYKDWLE ILSKDKDLLT NPLLPMLPVL
     QEPVRKHLTR WELYEDMATY DVTNTRRSLA DRGKLKSGIG LEDLRRHVED WVARGLVPSR
     N