ID   ATNL_EMENI              Reviewed;         306 AA.
AC   Q5AV06; A0A1U8QM29; C8V3X9;
DT   23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   25-MAY-2022, entry version 68.
DE   RecName: Full=Probable thioesterase atnL {ECO:0000303|PubMed:26563584};
DE            EC=2.3.1.- {ECO:0000305|PubMed:26563584};
DE   AltName: Full=Aspercryptin biosynthesis cluster protein L {ECO:0000303|PubMed:26563584};
GN   Name=atnL {ECO:0000303|PubMed:26563584}; ORFNames=ANIA_07874;
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, AND DISRUPTION PHENOTYPE.
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: Part of the gene cluster that mediates the biosynthesis of
CC       aspercryptins, linear lipopeptides built from six amino acids including
CC       2 highly unusual and nonproteogenic amino acids, 2-amino-octanoic acid
CC       (2aoa) and 2-amino-dodecanol (2adol) (PubMed:23248299, PubMed:27310134,
CC       PubMed:26563584). The core structure of aspercryptins is as follows:
CC       Ser/Ala-Thr-Ile/Val-2aoa-Asn-2adol (PubMed:27310134). The first step of
CC       aspercryptin biosynthesis is the generation of the fatty acid
CC       precursors, octanoic and dodecanoic acids, by the FAS subunits atnF and
CC       atnM (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   -!- INDUCTION: Expression is positively regulated by the aspercryptin
CC       cluser-specific transcription factor atnN (PubMed:27310134).
CC       {ECO:0000269|PubMed:27310134}.
CC   -!- DISRUPTION PHENOTYPE: Does not alter the yield of aspercryptin
CC       significantly (PubMed:26563584). {ECO:0000269|PubMed:26563584}.
CC   -!- SIMILARITY: Belongs to the lcsJ thioesterase family. {ECO:0000305}.
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DR   EMBL; BN001302; CBF73433.1; -; Genomic_DNA.
DR   EMBL; AACD01000135; EAA59528.1; -; Genomic_DNA.
DR   RefSeq; XP_681143.1; XM_676051.1.
DR   AlphaFoldDB; Q5AV06; -.
DR   SMR; Q5AV06; -.
DR   EnsemblFungi; CBF73433; CBF73433; ANIA_07874.
DR   EnsemblFungi; EAA59528; EAA59528; AN7874.2.
DR   GeneID; 2869212; -.
DR   KEGG; ani:AN7874.2; -.
DR   VEuPathDB; FungiDB:AN7874; -.
DR   eggNOG; KOG4366; Eukaryota.
DR   HOGENOM; CLU_040660_1_1_1; -.
DR   InParanoid; Q5AV06; -.
DR   OMA; ESRILCW; -.
DR   OrthoDB; 1195870at2759; -.
DR   Proteomes; UP000000560; Chromosome II.
DR   Proteomes; UP000005890; Unassembled WGS sequence.
DR   GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR029069; HotDog_dom_sf.
DR   SUPFAM; SSF54637; SSF54637; 1.
PE   2: Evidence at transcript level;
KW   Reference proteome; Transferase.
FT   CHAIN           1..306
FT                   /note="Probable thioesterase atnL"
FT                   /id="PRO_0000444140"
SQ   SEQUENCE   306 AA;  34588 MW;  F33F9D5BF0DEDE01 CRC64;
     MALPSSVESL LSTVWDFITI NRLLTGAGIY FLLLNAKGLP GVWHYRLFKG LFIELVWKRS
     TTPAPLLDSQ GRPRLYSYFV TECSNPVIEC DYNLHKSNST FFSDLDINRT QLMMTHFKHV
     LSTASMPRKT KTANGNGDDQ KRKRPLMMAM GGVSCLFHRE IKPLQRYEVW SRVLAWDEKW
     VYVVSYFVKK GSLSRDGNFK GDLDLDPKVN AKVVLASCMA RYVFKEGRIT VKPERVLQEC
     GLFPLAEEAV AGEKAEKASV DSWGKEQFEE ARQKGLVTAG KFSGLEVLPL MTGFGESGVL
     GRYNDF