ATND_EMENI
ID ATND_EMENI Reviewed; 314 AA.
AC C8V3Y7; Q5AUZ8;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Short chain dehydrogenase atnD {ECO:0000303|PubMed:26563584};
DE EC=1.1.1.- {ECO:0000305|PubMed:26563584};
DE AltName: Full=Aspercryptin biosynthesis cluster protein D {ECO:0000303|PubMed:26563584};
GN Name=atnD {ECO:0000303|PubMed:26563584}; ORFNames=AN7882, ANIA_11028;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP IDENTIFICATION OF THE CLUSTER.
RX PubMed=23248299; DOI=10.1073/pnas.1205532110;
RA Andersen M.R., Nielsen J.B., Klitgaard A., Petersen L.M., Zachariasen M.,
RA Hansen T.J., Blicher L.H., Gotfredsen C.H., Larsen T.O., Nielsen K.F.,
RA Mortensen U.H.;
RT "Accurate prediction of secondary metabolite gene clusters in filamentous
RT fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E99-E107(2013).
RN [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=27310134; DOI=10.1021/acschembio.6b00398;
RA Henke M.T., Soukup A.A., Goering A.W., McClure R.A., Thomson R.J.,
RA Keller N.P., Kelleher N.L.;
RT "New aspercryptins, lipopeptide natural products, revealed by HDAC
RT inhibition in Aspergillus nidulans.";
RL ACS Chem. Biol. 11:2117-2123(2016).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=26563584; DOI=10.1002/anie.201507097;
RA Chiang Y.M., Ahuja M., Oakley C.E., Entwistle R., Asokan A., Zutz C.,
RA Wang C.C., Oakley B.R.;
RT "Development of genetic dereplication strains in Aspergillus nidulans
RT results in the discovery of aspercryptin.";
RL Angew. Chem. Int. Ed. 55:1662-1665(2016).
CC -!- FUNCTION: Short chain dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of aspercryptins, linear lipopeptides built
CC from six amino acids including 2 highly unusual and nonproteogenic
CC amino acids, 2-amino-octanoic acid (2aoa) and 2-amino-dodecanol (2adol)
CC (PubMed:23248299, PubMed:27310134, PubMed:26563584). The core structure
CC of aspercryptins is as follows: Ser/Ala-Thr-Ile/Val-2aoa-Asn-2adol
CC (PubMed:27310134). The first step of aspercryptin biosynthesis is the
CC generation of the fatty acid precursors, octanoic and dodecanoic acids,
CC by the FAS subunits atnF and atnM (PubMed:27310134, PubMed:26563584).
CC The fatty acid precursors are likely transformed into the corresponding
CC alpha-amino fatty acids in three steps (PubMed:27310134,
CC PubMed:26563584). First, they are hydroxylated by the cytochrome P450
CC monooxygenase atnE, then oxidized to the corresponding alpha-keto acids
CC by the NAD(P)-dependent oxidoreductase atnD, and finally converted to
CC the alpha-amino fatty acids by the PLP-dependent aminotransferases atnH
CC or atnJ (PubMed:27310134, PubMed:26563584). the alpha-amino fatty
CC acids, 2-amino-octanoic and 2-amino-dodecanoic acids, are recognized,
CC activated, and covalently tethered to the NRPS atnA by its fourth and
CC sixth adenylation domains (PubMed:27310134). The second module of atnA
CC is the Thr module and contains an epimerase (E) domain responsible for
CC the epimerization of Thr to D-allo-Thr (PubMed:26563584). Additionally,
CC despite atnA having only one epimerase domain, the first amino acid of
CC aspercryptin A1 is D-Ser, suggesting that serine is either loaded
CC directly as D-Ser on the first module or that the epimerase domain in
CC the threonine module epimerizes both L-Ser and L-Thr (PubMed:27310134).
CC After condensation of the hexapeptide of aspercryptin, the C-terminal
CC reductase (TE) domain might be involved in the reductive release and
CC production of the aldehyde hexapeptide (PubMed:26563584). Further
CC reduction would generate aspercryptins (PubMed:27310134,
CC PubMed:26563584). The variety of aspercryptins produced reflects the
CC flexibiliy of the atnA NRPS, allowing incorporation of alanine instead
CC of serine, valine for isoleucine, and a C10 fatty amino alcohol instead
CC of the C12 version (PubMed:27310134). AtnB seems to be involved in the
CC selectivity for Ile versus Val by the third module (PubMed:26563584).
CC Moreover, type B, C and D aspercryptins have an additional N-terminal
CC cichorine, acetyl and propionyl group respectively (PubMed:27310134).
CC {ECO:0000269|PubMed:23248299, ECO:0000269|PubMed:26563584,
CC ECO:0000269|PubMed:27310134}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26563584}.
CC -!- INDUCTION: Expression is positively regulated by the aspercryptin
CC cluser-specific transcription factor atnN (PubMed:27310134).
CC {ECO:0000269|PubMed:27310134}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of aspercryptin
CC (PubMed:26563584). {ECO:0000269|PubMed:26563584}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA59536.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; BN001302; CBF73447.1; -; Genomic_DNA.
DR EMBL; AACD01000135; EAA59536.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_681151.1; XM_676059.1.
DR AlphaFoldDB; C8V3Y7; -.
DR SMR; C8V3Y7; -.
DR STRING; 227321.C8V3Y7; -.
DR EnsemblFungi; CBF73447; CBF73447; ANIA_11028.
DR EnsemblFungi; EAA59536; EAA59536; AN7882.2.
DR GeneID; 2869206; -.
DR KEGG; ani:AN7882.2; -.
DR eggNOG; KOG1208; Eukaryota.
DR HOGENOM; CLU_010194_44_4_1; -.
DR InParanoid; C8V3Y7; -.
DR OMA; WAEDNES; -.
DR OrthoDB; 1076292at2759; -.
DR Proteomes; UP000000560; Chromosome II.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..314
FT /note="Short chain dehydrogenase atnD"
FT /id="PRO_0000444135"
FT ACT_SITE 204
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 33..41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 60..61
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 112..114
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 204..208
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 240..242
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 314 AA; 34736 MW; 57F8EC9A5CFC6E89 CRC64;
MANPERSYLS RFFSSQFSKL PYPSQSFKDA VILVTGGNTG LGLEAARHFV RLQAATVILA
VRDLKKGEQA KLSIEESTKV QGVVEVWQVD LEDVRSVQSL AAKASSLPRL DVVVANAGIS
TNKWALVGDM ERTIQVNVLS TFLLILALLP KMQEQDIEGQ IRARPRVVVV SSEGHETTAF
AERKAARIFD ALRDQRQANM DERYDTSKLI QLYLVRALAE RLSRSDKPPV TLNAVSPGLC
KTGLLRETPL VARLLTGPVM AILARNAEEG SRTLVHAAAA NDGETNGKYL RDYLQRLYAA
KKATPRRRDC CRSF
