LNBA_ASPFN
ID LNBA_ASPFN Reviewed; 1007 AA.
AC B8NWW5;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Aldehyde reductase lnbA {ECO:0000303|PubMed:23281040};
DE EC=1.2.1.101 {ECO:0000269|PubMed:23281040};
DE AltName: Full=Lnb diastereomeric piperazines biosynthesis cluster protein A {ECO:0000303|PubMed:23281040};
DE AltName: Full=Non-canonical nonribosomal peptide synthetase lnbA {ECO:0000303|PubMed:23281040};
GN Name=lnaA {ECO:0000303|PubMed:23281040}; ORFNames=AFLA_121520;
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, 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 lnb 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 -!- 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; EQ963485; EED45923.1; -; Genomic_DNA.
DR RefSeq; XP_002384859.1; XM_002384818.1.
DR AlphaFoldDB; B8NWW5; -.
DR SMR; B8NWW5; -.
DR STRING; 5059.CADAFLAP00012724; -.
DR EnsemblFungi; EED45923; EED45923; AFLA_121520.
DR VEuPathDB; FungiDB:AFLA_121520; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_2_17_1; -.
DR OMA; YMIPQLQ; -.
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: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 Gene3D; 3.40.50.12780; -; 1.
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; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
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 SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 3: Inferred from homology;
KW Ligase; Multifunctional enzyme; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein.
FT CHAIN 1..1007
FT /note="Aldehyde reductase lnbA"
FT /id="PRO_0000446075"
FT DOMAIN 540..617
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 35..428
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23281040"
FT REGION 659..998
FT /note="Short-chain dehydrogenase/reductase (R) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23281040"
FT MOD_RES 577
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1007 AA; 110663 MW; 7AFB93DB0D19E92D CRC64;
MMLSNLLPSP EPLGADEYGL CVASNLGLGQ LFYRQVRQSP SSIAVVDDES SITYGQLHAW
AVRLAAKLSQ EGFVKEEAVG IVVQHGVADV VAQMAVIYAG GSCAPMDPTM RDQQIGQRLQ
RLNSRFILVD QSNRGRDLQF QQIVLEKHLP LTITDLCEEN EFPVTTDLSH RTHLIHTSGT
TSEPKAVQIA ARSILQVVFH APFEPLAVED VVAHANNSSF DVSLFDIWAP LLRGARIAIL
KKMVLLDLVV LAEHIDRLGI TVMATTTALL NLAASTLPTA FSKLRICFIG GEAANVSAIE
TVLRKGPPKM LINAYGPTEC CIFCLAHRVT PKDIQMGSVS IGMPIGHTIA YIADESGCAA
NEGELWIGGA GVSPGYINEP EKNAKSFPTI MMPSGEAARF YRTGDIVRRR DDGQIDYVGR
VDHQIKVRGF RIELEAIETS LLQTGLFAEV AAMGIQSPHQ GAGSVLVAYA TPKDPAHPPE
ISKALKILQD ILPEYMIPQL QLIEKMPLNS HAKVDRKGLK QLFCQRSTSL LKPVPKLPNT
LCQDTQTVLA SLWATILATP KSEYKESDDF FVLGGTSLQA SLLISQIRQV FRCEVSLLAL
YDNSTVGALA SIIDHAKGGH LKTVRDEREV WLADTKLADD LPAPMTTPVN WQRDIEGRIF
ITGATGFVGA FLLSDLLHMP SVHQIGCLVR APNSAAGMQR LRLALEKYNL WKDEFTNKLL
AFPGLLEDKY LGLEQARFNE LANWASVVFH LGARVNYTQP YSLHRPANTL GTINVVRFAC
TGRSKAVHYV SSISCFGPTG FFTGTASVGE DDSLLPHLEA LPYDHGYAQS QWVADQLLRR
LMDRGFPISI YRPGFITGHS QTGVCNPDDF FSRLMIACEQ MKSYPMLPNQ RKEFVPVDYV
NSVILHIAAS EHAVGRAYHI VPPNRDMSID MDATMDLLGD AVNSRIHALP YMEWIDRLAA
NPPVALQPLQ PMLAEKVHDA NYPGGLKFPT LDCSLLKKYI AHLRSAC
