ID   ACLP_ASPOR              Reviewed;        1625 AA.
AC   Q2UPA9;
DT   30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 1.
DT   25-MAY-2022, entry version 93.
DE   RecName: Full=Nonribosomal peptide synthetase aclP {ECO:0000303|PubMed:25302411};
DE            Short=NRPS aclP {ECO:0000303|PubMed:25302411};
DE            EC=6.3.2.- {ECO:0000269|PubMed:25302411};
DE   AltName: Full=Aspirochlorine biosynthesis protein P {ECO:0000303|PubMed:25302411};
GN   Name=aclP {ECO:0000303|PubMed:25302411}; ORFNames=AO090001000043;
OS   Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=510516;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 42149 / RIB 40;
RX   PubMed=16372010; DOI=10.1038/nature04300;
RA   Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA   Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA   Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA   Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA   Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA   Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA   Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA   Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA   Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA   Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA   Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA   Kikuchi H.;
RT   "Genome sequencing and analysis of Aspergillus oryzae.";
RL   Nature 438:1157-1161(2005).
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=25302411; DOI=10.1002/anie.201407624;
RA   Chankhamjon P., Boettger-Schmidt D., Scherlach K., Urbansky B., Lackner G.,
RA   Kalb D., Dahse H.M., Hoffmeister D., Hertweck C.;
RT   "Biosynthesis of the halogenated mycotoxin aspirochlorine in koji mold
RT   involves a cryptic amino acid conversion.";
RL   Angew. Chem. Int. Ed. 53:13409-13413(2014).
CC   -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC       that mediates the biosynthesis of aspirochlorine (or antibiotic
CC       A30641), an unusual halogenated spiro compound with distinctive
CC       antifungal properties due to selective inhibition of protein
CC       biosynthesis, and which is also active against bacteria, viruses, and
CC       murine tumor cells (PubMed:25302411). The non-ribosomal peptide
CC       synthetase (NRPS) aclP is responsible the formation of the
CC       diketopiperazine (DKP) core from the condensation of 2 phenylalanine
CC       residues (PubMed:25302411). One Phe residue is tailored into
CC       chlorotyrosine by hydroxylation and chlorination, whereas the second
CC       Phe undergoes an unprecedented C-C bond cleavage to be converted into
CC       glycine (PubMed:25302411). After formation of the DKP, sulfur is
CC       incorporated into the DKP by conjugation with glutathione by aclG,
CC       followed by its stepwise degradation to the thiol by aclI, aclJ and
CC       aclK, and the dithiol oxidation by aclT (PubMed:25302411). In addition,
CC       oxygenases (aclB, aclC, aclL and aclO) and O-methyltransferases (aclM
CC       and aclU) act as tailoring enzymes to produce the intermediate
CC       dechloroaspirochlorine (PubMed:25302411). Ultimately, chlorination of
CC       dechloroaspirochlorine by the halogenase aclH is the last step in the
CC       aspirochlorine pathway (PubMed:25302411).
CC       {ECO:0000269|PubMed:25302411}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:25302411}.
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 (By similarity). Each module is responsible for the recognition
CC       (via the A domain) and incorporation of a single amino acid into the
CC       growing peptide product (By similarity). Thus, an NRP synthetase is
CC       generally composed of one or more modules and can terminate in a
CC       thioesterase domain (TE) that releases the newly synthesized peptide
CC       from the enzyme (By similarity). Occasionally, epimerase (E) domains
CC       (responsible for L- to D-amino acid conversion) are present within the
CC       NRP synthetase (By similarity). AclP has the following architecture: T-
CC       C-A-T-C (PubMed:25302411). {ECO:0000250|UniProtKB:Q4WMJ7,
CC       ECO:0000269|PubMed:25302411}.
CC   -!- DISRUPTION PHENOTYPE: Completely abrogates the biosynthesis of
CC       aspirochlorine, but also of the intermediate dechloroaspirochlorine
CC       (PubMed:25302411). {ECO:0000269|PubMed:25302411}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; AP007154; BAE56606.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q2UPA9; -.
DR   SMR; Q2UPA9; -.
DR   STRING; 510516.Q2UPA9; -.
DR   EnsemblFungi; BAE56606; BAE56606; AO090001000043.
DR   HOGENOM; CLU_000022_0_5_1; -.
DR   OMA; AVYNCYG; -.
DR   Proteomes; UP000006564; Chromosome 2.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.30.559.10; -; 2.
DR   Gene3D; 3.40.50.12780; -; 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; IPR042099; ANL_N_sf.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR001242; Condensatn.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   1: Evidence at protein level;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN           1..1625
FT                   /note="Nonribosomal peptide synthetase aclP"
FT                   /id="PRO_0000441179"
FT   DOMAIN          47..123
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1096..1171
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          127..157
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          286..567
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          614..997
FT                   /note="Adenylation"
FT                   /evidence="ECO:0000255"
FT   REGION          1195..1585
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        136..157
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         84
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1131
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1625 AA;  179635 MW;  0F81B93188200E8D CRC64;
     MPLSGWPKGG YEVRLWYVHV PERYFIYMAA DWNPRHAPIN IGYPSRTTMN PSSQLLVQQL
     AAVLEVDTAE LDLNSGFVHN GGNSLSAVEF VSRSKSLGVS LSIASILSST NLRALFTDLL
     SSESNLIPIP DPSDDSDDLS NPSSSTGGSP RVATPISSNV STAAEDDYLT QGSVLTQYAT
     QSLSEMQASL LHGSLKSPGT NIIYHYETYQ TDVIPVLKRA WKTVIEGEPI FHSSLLDGSA
     RNQEYFTWSE VTVETEAEYR EQLQTLWLKS VSSSFKVVHW KRSPPASSQS TVIWAVHHAL
     VDGYSAMLLF CKVRRAIKGL PIVPGPSFSD VEKRIRVWRQ EHKSQGDEYW AGHAAQLDQA
     QGELLLPAPT PEGTSSAITE SEEVYVAPSV SNTQLHCVAK RLGVTLSTCY YAAWSLVLSL
     YADSASVVFG AVLAGRNLPL EGVDEVVGPL VNTLPLCLTL SRQQSAQDFL KNLFSRMVEL
     AEYQWTTPDN GYTRNFSSAM AMQVPGPECK DGVSPIEPPY TRQTTDVPLS INILTDGAAR
     FVYHTSQYSR ADIVRLGKYF QRALQLLLRP HRPIEECLQG LLGCVDLQTL MGFGNCSSSL
     TTTVAIKEDL VTLFESAVSR NPMDVAVQKG NCHLTYQELD THAGRVAATL RGYIQDGDVV
     CLHADRSVNW IVGIMGILKA GGVYCALDKA LPQEARETIF SASGSRLFLV PSLSDQSFCP
     TDCDRLLVVE DLVKDDNVPI THRDSPRPQT DAYLCFTSGS TGKPKGVMCL HQGLVAFQRD
     LEVRLFAQPG RRVAQIMSVA FDGSIHEIFS ALSYGAALVL QSGDDPFAHL SDVDSAILTP
     SMARVLNPAD FERLSTVSTK VYLVGEPVTQ DVCDRWSEQK TLYNMYGPTE GTCGATIKQL
     HPRQRVTIGP PNPSTRIYIM NQHQELVPPG VIGEIYIAGV QVARHYIGMP EQTAQRFVAD
     PIIRIGERMY KTGDRGYWSE DGEVVCLGRT DRQIKLRGFR LDLDDLETRM IRAFPAVTAV
     ALTRQGNHLI AAILPASTDV DAFSARVAQV LPPYATPRKI LALDEFPTTK AGKRDYLAIA
     KLSAQAPVST GRTLTSPMEK LVGDAFRDIL QLGKDVALHT HSSFRELGGH SLLQLLLATR
     ISQGVNRQVP LYVVAQHDRI DHLAAAIDSG LGLQQLVTTD PMGLGESAIA PIEREWWHKY
     QINESTSSFN VNFMAKIDDC LVDRARLVHA CNEVMARHRV LRSRYIFSRA AGRVVRQYSP
     LAPRVQAVKT VNPWVEVNRP FSLSRSAPIR AVVSDSYFIL TISHIVADLT TLQILLREIS
     SHYQGGSLPS IPHTYMNSTL WYEKPTSCDL DFWSDCLGQL PDTTHLLGHG GYRRGYRGRS
     ALCEVPPTTY QSMRHFLRQS SITAQQLSLA TIALCLDDPS VPMPTETDIV LGIPYINRKS
     QEDLDVVGLF LEPLPVRISF GQETHNHEKA SYLDTVQRSV RSSVGHAVHW DQLLEHLQVS
     TTPPDHPLFD VVVTFHSQSH SNGLELSAPG LRTCYTYAEG AKFRLLCEFS ALSEDRLLLR
     LEYDTDCFTE ENIQLLQARI PLALSLLVQN VPYDMIRQTL ACPPETQPVK VLKPDVVFGT
     PLSDI