ATNH_EMENI
ID ATNH_EMENI Reviewed; 396 AA.
AC Q5AV02; A0A1U8QYE8; C8V3Y3;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Branched-chain-amino-acid aminotransferase atnH {ECO:0000303|PubMed:26563584};
DE EC=2.6.1.- {ECO:0000305|PubMed:26563584};
DE AltName: Full=Aspercryptin biosynthesis cluster protein H {ECO:0000303|PubMed:26563584};
GN Name=atnH {ECO:0000303|PubMed:26563584}; ORFNames=ANIA_07878;
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: Branched-chain-amino-acid aminotransferase; part of the gene
CC cluster that mediates the biosynthesis of aspercryptins, linear
CC lipopeptides built from six amino acids including 2 highly unusual and
CC nonproteogenic amino acids, 2-amino-octanoic acid (2aoa) and 2-amino-
CC dodecanol (2adol) (PubMed:23248299, PubMed:27310134, PubMed:26563584).
CC The core structure of aspercryptins is as follows: Ser/Ala-Thr-Ile/Val-
CC 2aoa-Asn-2adol (PubMed:27310134). The first step of aspercryptin
CC biosynthesis is the generation of the fatty acid precursors, octanoic
CC and dodecanoic acids, by the FAS subunits atnF and atnM
CC (PubMed:27310134, PubMed:26563584). The fatty acid precursors are
CC likely transformed into the corresponding alpha-amino fatty acids in
CC three steps (PubMed:27310134, PubMed:26563584). First, they are
CC hydroxylated by the cytochrome P450 monooxygenase atnE, then oxidized
CC to the corresponding alpha-keto acids by the NAD(P)-dependent
CC oxidoreductase atnD, and finally converted to the alpha-amino fatty
CC acids by the PLP-dependent aminotransferases atnH or atnJ
CC (PubMed:27310134, PubMed:26563584). the alpha-amino fatty acids, 2-
CC amino-octanoic and 2-amino-dodecanoic acids, are recognized, activated,
CC and covalently tethered to the NRPS atnA by its fourth and sixth
CC adenylation domains (PubMed:27310134). The second module of atnA is the
CC Thr module and contains an epimerase (E) domain responsible for the
CC 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 -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P19938};
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: Eliminates approximately 40% of aspercryptin
CC production (PubMed:26563584). {ECO:0000269|PubMed:26563584}.
CC -!- SIMILARITY: Belongs to the class-IV pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000255|RuleBase:RU004106}.
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DR EMBL; BN001302; CBF73440.1; -; Genomic_DNA.
DR EMBL; AACD01000135; EAA59532.1; -; Genomic_DNA.
DR RefSeq; XP_681147.1; XM_676055.1.
DR AlphaFoldDB; Q5AV02; -.
DR SMR; Q5AV02; -.
DR STRING; 162425.CADANIAP00003894; -.
DR EnsemblFungi; CBF73440; CBF73440; ANIA_07878.
DR EnsemblFungi; EAA59532; EAA59532; AN7878.2.
DR GeneID; 2869297; -.
DR KEGG; ani:AN7878.2; -.
DR eggNOG; KOG0975; Eukaryota.
DR HOGENOM; CLU_031922_0_2_1; -.
DR InParanoid; Q5AV02; -.
DR OMA; RIEYKER; -.
DR OrthoDB; 853728at2759; -.
DR Proteomes; UP000000560; Chromosome II.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004084; F:branched-chain-amino-acid transaminase activity; IBA:GO_Central.
DR GO; GO:0009098; P:leucine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009099; P:valine biosynthetic process; IBA:GO_Central.
DR CDD; cd01557; BCAT_beta_family; 1.
DR Gene3D; 3.20.10.10; -; 1.
DR Gene3D; 3.30.470.10; -; 1.
DR InterPro; IPR001544; Aminotrans_IV.
DR InterPro; IPR018300; Aminotrans_IV_CS.
DR InterPro; IPR036038; Aminotransferase-like.
DR InterPro; IPR005786; B_amino_transII.
DR InterPro; IPR043132; BCAT-like_C.
DR InterPro; IPR043131; BCAT-like_N.
DR InterPro; IPR033939; BCAT_family.
DR PANTHER; PTHR11825; PTHR11825; 1.
DR Pfam; PF01063; Aminotran_4; 1.
DR PIRSF; PIRSF006468; BCAT1; 1.
DR SUPFAM; SSF56752; SSF56752; 1.
DR TIGRFAMs; TIGR01123; ilvE_II; 1.
DR PROSITE; PS00770; AA_TRANSFER_CLASS_4; 1.
PE 2: Evidence at transcript level;
KW Amino-acid biosynthesis; Aminotransferase;
KW Branched-chain amino acid biosynthesis; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT CHAIN 1..396
FT /note="Branched-chain-amino-acid aminotransferase atnH"
FT /id="PRO_0000444131"
FT BINDING 122
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P19938"
FT MOD_RES 224
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P19938"
SQ SEQUENCE 396 AA; 44244 MW; 48CCE97D80E9D4B6 CRC64;
MARLLNRWHL PALVRRHYSS RFQSLRIEKT QSPKPLPDST ELQFGRSFTG KYPSQTRNHI
LKLEWTTTQG WSDAQITPYD NLRLDPASCV LHYAFTCFEG MKAYKDPHGN ARLFRPEENL
ARLNRSAARL ALPTFEESGV LEFLAKYVDL EKRFIPHLPG HSLYLRPTLL GTDASISVSR
PRSALLFVIA SPMGDYFANG MKAVTLQATR SPVRAWPGGV GEFKVGGNYA PSIVPQEEAA
EAGSQQNLWL LADRESGEEF VTEAGTMNLF VVWVSSSTGK KELVTPPLDG TILPGVTRMS
ILELARERLE GDRSGIEVVE RRITMRELAA ASKEGRLLEV FGAGTAVVVS PVRSIRWGDQ
CISCGLRDGE EAGPMSLQMK TWLEEVQYGL VEHPWR
