ID   CTVB_ASPTN              Reviewed;         229 AA.
AC   Q0C9L6;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 61.
DE   RecName: Full=Methyltransferase ctvB {ECO:0000303|PubMed:26954888};
DE            EC=2.1.1.- {ECO:0000269|PubMed:26954888};
DE   AltName: Full=Citreoviridin biosynthesis protein B {ECO:0000305};
GN   Name=ctvB {ECO:0000303|PubMed:26954888}; ORFNames=ATEG_09618;
OS   Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=341663;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NIH 2624 / FGSC A1156;
RA   Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA   Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA   Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA   Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA   Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA   Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA   Nierman W.C., Milne T., Madden K.;
RT   "Annotation of the Aspergillus terreus NIH2624 genome.";
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   BIOTECHNOLOGY.
RX   PubMed=2523213; DOI=10.1016/0003-9861(89)90554-7;
RA   Sayood S.F., Suh H., Wilcox C.S., Schuster S.M.;
RT   "Effect of citreoviridin and isocitreoviridin on beef heart mitochondrial
RT   ATPase.";
RL   Arch. Biochem. Biophys. 270:714-721(1989).
RN   [3]
RP   BIOTECHNOLOGY.
RX   PubMed=22753871; DOI=10.1182/blood-2011-12-399063;
RA   Yavlovich A., Viard M., Zhou M., Veenstra T.D., Wang J.M., Gong W.,
RA   Heldman E., Blumenthal R., Raviv Y.;
RT   "Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting
RT   cells to CD4(+) target cells.";
RL   Blood 120:1246-1253(2012).
RN   [4]
RP   BIOTECHNOLOGY.
RX   PubMed=22822083; DOI=10.1158/0008-5472.can-12-0567;
RA   Chang H.Y., Huang H.C., Huang T.C., Yang P.C., Wang Y.C., Juan H.F.;
RT   "Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by
RT   activating the unfolded protein response.";
RL   Cancer Res. 72:4696-4706(2012).
RN   [5]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=26954888; DOI=10.1021/acs.orglett.6b00299;
RA   Lin T.S., Chiang Y.M., Wang C.C.;
RT   "Biosynthetic pathway of the reduced polyketide product citreoviridin in
RT   Aspergillus terreus var. aureus revealed by heterologous expression in
RT   Aspergillus nidulans.";
RL   Org. Lett. 18:1366-1369(2016).
CC   -!- FUNCTION: Methyltransferase; part of the gene cluster that mediates the
CC       biosynthesis of citreoviridin, an inhibitor of the of F1-ATPase beta-
CC       subunit (PubMed:26954888). The HR-PKS ctvA accepts acetyl-CoA as the
CC       starter unit and catalyzes eight iterations of malonyl-CoA extension
CC       and four iterations of SAM-dependent methylation at C4, C12, C14, and
CC       C16 (PubMed:26954888). The KR and DH domains selectively act on the
CC       first six iterations to generate the hexaene chain (PubMed:26954888).
CC       In the last three iterations, the KR and DH domains terminate their
CC       functions to yield a beta,delta-diketo ester moiety, which then
CC       undergoes intramolecular cyclization to yield an alpha-pyrone
CC       intermediate (PubMed:26954888). Subsequently, ctvB methylates the
CC       alpha-pyrone hydroxyl group to generate citreomontanin
CC       (PubMed:26954888). In order to form the tetrahydrofuran ring with the
CC       correct stereochemistry, the terminal alkenes of citreomontanin need to
CC       undergo isomerization to yield a (17Z)-hexaene, a step that could be
CC       catalyzed by ctvC (PubMed:26954888). The (17Z)-hexaene then undergoes
CC       bisepoxidation by ctvC to form a (17R,16R,15S,14R)-bisepoxide moiety
CC       (PubMed:26954888). Lastly, ctvD acts as a regioselective hydrolase to
CC       form the tetrahydrofuran ring with the substituents in the correct
CC       absolute configuration, completing the biosynthesis of citreoviridin
CC       (PubMed:26954888). {ECO:0000269|PubMed:26954888}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:26954888}.
CC   -!- BIOTECHNOLOGY: Citreoviridin inhibits mitochondrial oxidative
CC       phosphorylation by binding to the beta-subunit of F1-ATPase
CC       (PubMed:2523213). Ectopic mitochondrial ATP synthase is a factor that
CC       mediates HIV-1 transfer between antigen-presenting cells (APCs) and
CC       CD4+ target cells, and citreoviridin can completely block antigen-
CC       presenting cell (APC)-mediated transfer of HIV-1 at the APC-target
CC       cells (PubMed:22753871). Inhibition of Ectopic mitochondrial ATP
CC       synthase by citreoviridin can also lead to suppression of cancer growth
CC       by activating the unfolded protein response (PubMed:22822083).
CC       {ECO:0000269|PubMed:22753871, ECO:0000269|PubMed:22822083,
CC       ECO:0000269|PubMed:2523213}.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC       {ECO:0000255}.
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DR   EMBL; CH476608; EAU29809.1; -; Genomic_DNA.
DR   RefSeq; XP_001218240.1; XM_001218239.1.
DR   AlphaFoldDB; Q0C9L6; -.
DR   EnsemblFungi; EAU29809; EAU29809; ATEG_09618.
DR   GeneID; 4354536; -.
DR   VEuPathDB; FungiDB:ATEG_09618; -.
DR   eggNOG; ENOG502SNYW; Eukaryota.
DR   HOGENOM; CLU_046029_0_0_1; -.
DR   OMA; ANVGPRH; -.
DR   OrthoDB; 1170760at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR016584; MeTrfase_VrtF.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   PIRSF; PIRSF011491; Mtase_YbcY_prd; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   1: Evidence at protein level;
KW   Methyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..229
FT                   /note="Methyltransferase ctvB"
FT                   /id="PRO_0000437745"
SQ   SEQUENCE   229 AA;  26593 MW;  74D6C07595D0E94B CRC64;
     MTFYQLSDAE GADNYYNPLL LWWYDFWVHW VSALFAWKCS SKNILLPFFL SNIGSRHCDV
     GVGTGYYLSA VRKRQPSWPQ DKLTLVDFHI RCLRKAANRV GIADRTECVL ANILEPIPIQ
     PERQFDSISL MYVLHCLPGA SKDKGRVFAN LKPLLKDSGT LFGSTLLCRG VRQNWFNWLL
     QRIYNAVDMF QNRADFPDDF VRALEEEFEE VESVIIGTVL MFKARKPRR