ID   DTXS2_METRA             Reviewed;         516 AA.
AC   E9FCP5;
DT   08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT   04-MAR-2015, sequence version 2.
DT   03-AUG-2022, entry version 42.
DE   RecName: Full=Cytochrome P450 monooxygenase dtxS2 {ECO:0000305};
DE   AltName: Full=Destruxin synthesis protein 1 {ECO:0000303|PubMed:22232661};
GN   Name=dtxS2 {ECO:0000303|PubMed:22232661}; ORFNames=MAA_10044;
OS   Metarhizium robertsii (strain ARSEF 23 / ATCC MYA-3075) (Metarhizium
OS   anisopliae (strain ARSEF 23)).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Metarhizium.
OX   NCBI_TaxID=655844;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ARSEF 23 / ATCC MYA-3075;
RX   PubMed=21253567; DOI=10.1371/journal.pgen.1001264;
RA   Gao Q., Jin K., Ying S.-H., Zhang Y., Xiao G., Shang Y., Duan Z., Hu X.,
RA   Xie X.-Q., Zhou G., Peng G., Luo Z., Huang W., Wang B., Fang W., Wang S.,
RA   Zhong Y., Ma L.-J., St Leger R.J., Zhao G.-P., Pei Y., Feng M.-G., Xia Y.,
RA   Wang C.;
RT   "Genome sequencing and comparative transcriptomics of the model
RT   entomopathogenic fungi Metarhizium anisopliae and M. acridum.";
RL   PLoS Genet. 7:E1001264-E1001264(2011).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=ARSEF 23 / ATCC MYA-3075;
RX   PubMed=25368161; DOI=10.1073/pnas.1412662111;
RA   Hu X., Xiao G., Zheng P., Shang Y., Su Y., Zhang X., Liu X., Zhan S.,
RA   St Leger R.J., Wang C.;
RT   "Trajectory and genomic determinants of fungal-pathogen speciation and host
RT   adaptation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:16796-16801(2014).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22232661; DOI=10.1073/pnas.1115983109;
RA   Wang B., Kang Q., Lu Y., Bai L., Wang C.;
RT   "Unveiling the biosynthetic puzzle of destruxins in Metarhizium species.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:1287-1292(2012).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of destruxins, insecticidal cyclic
CC       hexadepsipeptides which induce flaccid paralysis and visceral muscle
CC       contraction in insects through targeting the calcium channels and
CC       vacuolar-type ATPases (PubMed:22232661). The aldo-keto reductase dtxS3
CC       converts alpha-ketoisocaproic acid from deaminated leucine into alpha-
CC       hydroxyisocaproic acid (HIC), which is the first substrate for
CC       destruxin assembly by dtxS1 (PubMed:22232661). L-aspartate
CC       decarboxylase dtxS4 converts aspartic acid into beta-alanine, the last
CC       substrate for the destruxin assembly line performed by dtxS1
CC       (PubMed:22232661). The nonribosomal peptide synthetase dtxS1
CC       synthesizes destruxins B and B2, whereas the cytochrome P450
CC       monooxygenase dtxS2 is required to convert destruxin B into other
CC       destruxin derivatives, including destructins C, D, A and E
CC       (PubMed:22232661). Destruxin E-diol (ED) is further produced in a non-
CC       enzymatic manner from destruxin E (PubMed:22232661). Destruxins play an
CC       important role in virulence and escape from insect host immune defenses
CC       (PubMed:22232661). {ECO:0000269|PubMed:22232661}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:22232661}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Leads to the accumulation of intermediary
CC       metabolites destruxin B, destruxin B2 and desmethyl-B
CC       (PubMed:22232661). {ECO:0000269|PubMed:22232661}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; ADNJ02000010; EFY94501.2; -; Genomic_DNA.
DR   RefSeq; XP_007826233.2; XM_007828042.2.
DR   AlphaFoldDB; E9FCP5; -.
DR   SMR; E9FCP5; -.
DR   EnsemblFungi; EFY94501; EFY94501; MAA_10044.
DR   GeneID; 19264330; -.
DR   KEGG; maj:MAA_10044; -.
DR   HOGENOM; CLU_001570_14_11_1; -.
DR   Proteomes; UP000002498; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..516
FT                   /note="Cytochrome P450 monooxygenase dtxS2"
FT                   /id="PRO_0000436437"
FT   TRANSMEM        23..43
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        229..249
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         458
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
FT   CARBOHYD        187
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   516 AA;  59594 MW;  AF808943771E62C5 CRC64;
     MLRIPGKSLG YHEDISLTPW QAILASVIVL LGLKVATILY TAFYNVFLHP LRRFPGPVTW
     IAAPWMKSIS HIRGQQDHQI VKLHQKLGHI IRVGPDTLSF TEMSAWRDIY GTGHAELPKH
     IYKGSGMEER PNIITAHSRD HHRFRKAMTP ALTPEAITHE EALIKGYVDM LIEHLHKFAK
     SSDPYVNVSQ WYTMTTFDIF GDLCYGESFN SLATGKQHLW LKSMSSMKVL VPLLVFPYIS
     WLLVWWLLSP EQQRSLSDHQ KRSYELTMKR IANRDTHPRH DFMTFMLRNR GEDQGVTDHE
     LASNSDIVIS AGSETTSTAL TGITFFLCSN PDAMARCAKE VREAFKSDDE ITFKATAELP
     FMLACIEETL RMYPPVPTSL IRRTLPGRPT LIAGELIPEN TIVGVHHLAT YRSERNFFDA
     KAFRPERWLA ETRNDPKSPF KDDRLDAVRP FSYGPRNCIG RNLAYHEMRL ILAKLLWHFD
     LKLKPGYEDW GFKQRTFQLW EKPKLVVEFK ERQFQV