ID   LNAA_ASPFN              Reviewed;        1042 AA.
AC   B8NTZ9;
DT   16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 74.
DE   RecName: Full=Aldehyde reductase lnaA {ECO:0000303|PubMed:23281040};
DE            EC=1.2.1.101 {ECO:0000269|PubMed:23281040};
DE   AltName: Full=Lna diastereomeric piperazines biosynthesis cluster protein A {ECO:0000303|PubMed:23281040};
DE   AltName: Full=Non-canonical nonribosomal peptide synthetase lnaA {ECO:0000303|PubMed:23281040};
GN   Name=lnaA {ECO:0000303|PubMed:23281040}; ORFNames=AFLA_101700;
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, FUNCTION, SUBSTRATE SPECIFICITY, DOMAIN, DISRUPTION
RP   PHENOTYPE, INDUCTION, AND PATHWAY.
RX   PubMed=23281040; DOI=10.1002/anie.201207456;
RA   Forseth R.R., Amaike S., Schwenk D., Affeldt K.J., Hoffmeister D.,
RA   Schroeder F.C., Keller N.P.;
RT   "Homologous NRPS-like gene clusters mediate redundant small-molecule
RT   biosynthesis in Aspergillus flavus.";
RL   Angew. Chem. Int. Ed. 52:1590-1594(2013).
CC   -!- FUNCTION: Non-canonical nonribosomal peptide synthetase; part of the
CC       lna gene cluster that mediates the biosynthesis of diastereomeric
CC       piperazines. Lna and lnb clusters encode sets of enzymes that produce
CC       overlapping sets of previously undescribed metabolites such as
CC       piperazinomycin-like metabolites or morpholine (PubMed:23281040). The
CC       lna and lnb biosynthetic pathways appear to be part of a signaling
CC       network that controls the formation of sclerotia, a resilient
CC       overwintering structure (PubMed:23281040). One primary function of the
CC       non-canonical nonribosomal peptide synthetases lnaA and lnbA consists
CC       in the reduction of L-tyrosine (PubMed:23281040). The presence in the
CC       clusters of tailoring enzymes such as the oxidoreductases lnaB, lnbB,
CC       lnaE or lnbE, as well as of the cytochrome P450 monooxygenases lnaC,
CC       lnaD, or lnbC, might explain formation of various diastereomeric
CC       piperazines (PubMed:23281040). {ECO:0000269|PubMed:23281040}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AMP + diphosphate + L-tyrosinal + NADP(+) = ATP + H(+) + L-
CC         tyrosine + NADPH; Xref=Rhea:RHEA:57412, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:141668,
CC         ChEBI:CHEBI:456215; EC=1.2.1.101;
CC         Evidence={ECO:0000269|PubMed:23281040};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:57414;
CC         Evidence={ECO:0000269|PubMed:23281040};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:23281040}.
CC   -!- INDUCTION: Expression is regulated by a complex signaling network which
CC       may include cross-pathway interactions mediated by sensing of the
CC       cluster final products or shared biosynthetic intermediates.
CC       {ECO:0000269|PubMed:23281040}.
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. LnaA contains an amino acid
CC       adenylation 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.
CC       {ECO:0000305|PubMed:23281040}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of piperazines and
CC       suppresses the formation of sclerotia when lnbA is also disrupted.
CC       {ECO:0000269|PubMed:23281040}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; EQ963484; EED46506.1; -; Genomic_DNA.
DR   RefSeq; XP_002384042.1; XM_002384001.1.
DR   AlphaFoldDB; B8NTZ9; -.
DR   SMR; B8NTZ9; -.
DR   STRING; 5059.CADAFLAP00011907; -.
DR   EnsemblFungi; EED46506; EED46506; AFLA_101700.
DR   VEuPathDB; FungiDB:AFLA_101700; -.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_2_17_1; -.
DR   OMA; RTIARIC; -.
DR   BRENDA; 1.2.1.101; 506.
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; 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; IPR010080; Thioester_reductase-like_dom.
DR   Pfam; PF00501; AMP-binding; 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.
PE   2: Evidence at transcript level;
KW   Ligase; Multifunctional enzyme; Oxidoreductase; Phosphopantetheine;
KW   Phosphoprotein.
FT   CHAIN           1..1042
FT                   /note="Aldehyde reductase lnaA"
FT                   /id="PRO_0000446074"
FT   DOMAIN          532..609
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:23281040"
FT   REGION          29..425
FT                   /note="Adenylation (A) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:23281040"
FT   REGION          655..897
FT                   /note="Short-chain dehydrogenase/reductase (R) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:23281040"
FT   MOD_RES         569
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1042 AA;  115511 MW;  7C504E0CF3A8352C CRC64;
     MPSQVLTHEE EYDLAVRQGK GLAQQFFDHA FLNPSAMAVI DGDTNLTYQD LHERAAMLAR
     ELQRGNLHTE EPVGVVVQHG ISDVVAQMAI LYAAGTCVPM DPTLPDLQIK GRLDRLKARY
     ILVDRANQHR DLPFHPLIVD DSSASFSKSS HVRDNEEPMQ ITLEHRTHII HTSGTTSEPK
     AVQIAARSIL QVVFHAPFEP LYPTDRVAHV NNSSFDVSLF DIWAPLLRGA CIVVVSKVTL
     LDLETLAAYI DRQGITVMAT TTAILNLAAS VYPRAFEKLR LCFIGGEAAN ISAIETIFQA
     GPPTQLINAY GPTECCIFCL AHRVTIADVQ AGVVSIGKPI GRTVAYICDE AGRPVPDGHE
     GELLIGGAGV SPGYINQPDK NRASFVAIEG SDCQRFYRTG DIVRRRVSNG QIDYVGRRDH
     QVKVRGFRIE LEAVESAIMK TGQFSEAVAL KVEAGSEGAG SILVAFAVAL SGTKPHAVLS
     AVDMLKAVLP DYMVPKIELI SKMPVNSHAK VDRKYLQQLF RNRWAEQHID MDNEDSTRGK
     LANLWASILG VPVPASNDNA DFFLLGATSM QASLLISRIQ KTFNVQVSLL TLYDNSSLIR
     LAGILEERIL GTQESFCKES ERHMWLEDSK LADSLVPPSD PPVDWCRDTE GRVFLTGATG
     FVGSFLLADL LRQPNVHQVG CLVRAVDPAT GLRRLQNGLA KYDLWEDQFR YKLLPLCGTL
     EDRYLGLGPD RFEEIAHWAS VIFHLGARVN YTQPYSLHRP ANVQGTVNVL RLACAGRSKV
     LHYVSSISCF GPTGFITGTR TVMENEPLPR HLEALPYDHG YAQSQWVVEN MLQRLMDNGF
     PIVVYRPGFI TGHSQTGACN PDDFLSRLII ACGEMGSYPL LPNQRKEFVP VDYVNAVILH
     IASSTATAVG RVYHIVPPNR DLSLDMNDSM ELVGSLAEGN ESSVRGVSYQ QWVQELDRQS
     PERLRPLQPM LTEKLYQGLT RWELYENMPV YDTTNTRQAL ESYPGGLKFP VLDSELMQKY
     IRYLQIRSAS PKEENPLNGT DS