ID   ACLH_ASPOR              Reviewed;         549 AA.
AC   Q2UPC7;
DT   30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 1.
DT   03-AUG-2022, entry version 77.
DE   RecName: Full=Flavine halogenase aclH {ECO:0000303|PubMed:25302411};
DE            EC=1.14.14.- {ECO:0000269|PubMed:25302411};
DE   AltName: Full=Aspirochlorine biosynthesis protein H {ECO:0000303|PubMed:25302411};
DE   Flags: Precursor;
GN   Name=aclH {ECO:0000303|PubMed:25302411}; ORFNames=AO090001000024;
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, 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: Flavine halogenase; part of the gene cluster that mediates
CC       the biosynthesis of aspirochlorine (or antibiotic A30641), an unusual
CC       halogenated spiro compound with distinctive antifungal properties due
CC       to selective inhibition of protein biosynthesis, and which is also
CC       active against bacteria, viruses, and murine tumor cells
CC       (PubMed:25302411). The non-ribosomal peptide synthetase (NRPS) aclP is
CC       responsible the formation of the diketopiperazine (DKP) core from the
CC       condensation of 2 phenylalanine residues (PubMed:25302411). One Phe
CC       residue is tailored into chlorotyrosine by hydroxylation and
CC       chlorination, whereas the second Phe undergoes an unprecedented C-C
CC       bond cleavage to be converted into glycine (PubMed:25302411). After
CC       formation of the DKP, sulfur is incorporated into the DKP by
CC       conjugation with glutathione by aclG, followed by its stepwise
CC       degradation to the thiol by aclI, aclJ and aclK, and the dithiol
CC       oxidation by aclT (PubMed:25302411). In addition, oxygenases (aclB,
CC       aclC, aclL and aclO) and O-methyltransferases (aclM and aclU) act as
CC       tailoring enzymes to produce the intermediate dechloroaspirochlorine
CC       (PubMed:25302411). Ultimately, chlorination of dechloroaspirochlorine
CC       by the halogenase aclH is the last step in the aspirochlorine pathway
CC       (PubMed:25302411). {ECO:0000269|PubMed:25302411}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P95480};
CC       Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P95480};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:25302411}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes completely the formation of
CC       aspirochlorine and leads to the accumulation of dechloroaspirochlorine
CC       (PubMed:25302411). {ECO:0000269|PubMed:25302411}.
CC   -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC       {ECO:0000305}.
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DR   EMBL; AP007154; BAE56588.1; -; Genomic_DNA.
DR   RefSeq; XP_001818590.1; XM_001818538.2.
DR   AlphaFoldDB; Q2UPC7; -.
DR   SMR; Q2UPC7; -.
DR   EnsemblFungi; BAE56588; BAE56588; AO090001000024.
DR   GeneID; 5990561; -.
DR   KEGG; aor:AO090001000024; -.
DR   HOGENOM; CLU_024648_4_2_1; -.
DR   OMA; REAYEQY; -.
DR   Proteomes; UP000006564; Chromosome 2.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR006905; Flavin_halogenase.
DR   Pfam; PF04820; Trp_halogenase; 2.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   1: Evidence at protein level;
KW   FAD; Flavoprotein; Glycoprotein; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..549
FT                   /note="Flavine halogenase aclH"
FT                   /id="PRO_0000441192"
FT   BINDING         14..17
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   BINDING         37..48
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   BINDING         328..329
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        419
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        458
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        498
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   549 AA;  59881 MW;  260A58D9CBEE8A8D CRC64;
     MSIPNRCTVL VVGGGPAGSY AAAALAREGV DTVLLEADVF PRYHIGESML PSIRHFLRFI
     DLDSKFDSYG FVNKNGAAFK LNSKPEAYTD FIAAGGPGSH AWNVVRSEAD HLMFKHAGEN
     GAQVFDGVKV NSIEFEQIDG LTVDPSLSEL GRPVSATWSC KATGGKGSIT FEYLIDATGR
     AGLVSTKYMK NRRYNQGLKN VASWGYWSNA GSYGVGTPRE GDPYFEAIED GSGWVWLIPL
     HNGTTSIGVV MNQEAATAKK RETGATTKDL YLNTIKNTPG VWQLLDKAEL QSDLKSASDW
     SYNASSYASP YLRIVGDAGC FIDPFFSSGV HLALASGLSA ALTIRAAQRG DCDEQAAVSW
     HSKKVAEGYT RFLLVVMSAL KQISDREKPV LTDFDEDSFN RAFDFFRPII QGTADVDKNL
     TQAEIAQTIE FCVQAFQTAS TDEQDAVMTK VAAINSQNGT EGALRELHAS LSADERRTLT
     TIQARQIIRS EDQMNIDNFT IDVIDGMVPR LERSSLGLAR FVPKAQTSRE DGLRATLGLP
     EKQKSIFSY