TERB_ASPTN
ID TERB_ASPTN Reviewed; 952 AA.
AC Q0D1P0;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=6-hydroxymellein synthase terB {ECO:0000303|PubMed:24816227};
DE EC=2.3.1.- {ECO:0000269|PubMed:24816227};
DE AltName: Full=Terrein biosynthesis cluster protein terB {ECO:0000303|PubMed:24816227};
GN Name=terB {ECO:0000303|PubMed:24816227}; ORFNames=ATEG_00144;
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=15558216; DOI=10.1007/s00018-004-4341-3;
RA Park S.H., Kim D.S., Kim W.G., Ryoo I.J., Lee D.H., Huh C.H., Youn S.W.,
RA Yoo I.D., Park K.C.;
RT "Terrein: a new melanogenesis inhibitor and its mechanism.";
RL Cell. Mol. Life Sci. 61:2878-2885(2004).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=15603975; DOI=10.1016/j.bmcl.2004.10.057;
RA Lee S., Kim W.G., Kim E., Ryoo I.J., Lee H.K., Kim J.N., Jung S.H.,
RA Yoo I.D.;
RT "Synthesis and melanin biosynthesis inhibitory activity of (+/-)-terrein
RT produced by Penicillium sp. 20135.";
RL Bioorg. Med. Chem. Lett. 15:471-473(2005).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=18776656; DOI=10.1038/ja.2008.60;
RA Arakawa M., Someno T., Kawada M., Ikeda D.;
RT "A new terrein glucoside, a novel inhibitor of angiogenin secretion in
RT tumor angiogenesis.";
RL J. Antibiot. 61:442-448(2008).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=18358890; DOI=10.1016/j.joen.2008.01.015;
RA Lee J.C., Yu M.K., Lee R., Lee Y.H., Jeon J.G., Lee M.H., Jhee E.C.,
RA Yoo I.D., Yi H.K.;
RT "Terrein reduces pulpal inflammation in human dental pulp cells.";
RL J. Endod. 34:433-437(2008).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=19493001; DOI=10.1111/j.1600-0625.2009.00847.x;
RA Park S.H., Kim D.S., Lee H.K., Kwon S.B., Lee S., Ryoo I.J., Kim W.G.,
RA Yoo I.D., Park K.C.;
RT "Long-term suppression of tyrosinase by terrein via tyrosinase degradation
RT and its decreased expression.";
RL Exp. Dermatol. 18:562-566(2009).
RN [7]
RP BIOTECHNOLOGY.
RX PubMed=21104936; DOI=10.1002/cbf.1708;
RA Lee Y.H., Lee N.H., Bhattarai G., Oh Y.T., Yu M.K., Yoo I.D., Jhee E.C.,
RA Yi H.K.;
RT "Enhancement of osteoblast biocompatibility on titanium surface with
RT Terrein treatment.";
RL Cell Biochem. Funct. 28:678-685(2010).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=23417151; DOI=10.3892/or.2013.2288;
RA Porameesanaporn Y., Uthaisang-Tanechpongtamb W., Jarintanan F.,
RA Jongrungruangchok S., Thanomsub Wongsatayanon B.;
RT "Terrein induces apoptosis in HeLa human cervical carcinoma cells through
RT p53 and ERK regulation.";
RL Oncol. Rep. 29:1600-1608(2013).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX PubMed=24816227; DOI=10.1016/j.chembiol.2014.03.010;
RA Zaehle C., Gressler M., Shelest E., Geib E., Hertweck C., Brock M.;
RT "Terrein biosynthesis in Aspergillus terreus and its impact on
RT phytotoxicity.";
RL Chem. Biol. 21:719-731(2014).
RN [10]
RP BIOTECHNOLOGY.
RX PubMed=25318762; DOI=10.3892/ijmm.2014.1964;
RA Chen Y.F., Wang S.Y., Shen H., Yao X.F., Zhang F.L., Lai D.;
RT "The marine-derived fungal metabolite, terrein, inhibits cell proliferation
RT and induces cell cycle arrest in human ovarian cancer cells.";
RL Int. J. Mol. Med. 34:1591-1598(2014).
RN [11]
RP BIOTECHNOLOGY.
RX PubMed=26416516; DOI=10.1002/cbf.3145;
RA Lee Y.H., Lee S.J., Jung J.E., Kim J.S., Lee N.H., Yi H.K.;
RT "Terrein reduces age-related inflammation induced by oxidative stress
RT through Nrf2/ERK1/2/HO-1 signalling in aged HDF cells.";
RL Cell Biochem. Funct. 33:479-486(2015).
RN [12]
RP INDUCTION.
RX PubMed=26173180; DOI=10.7554/elife.07861;
RA Gressler M., Meyer F., Heine D., Hortschansky P., Hertweck C., Brock M.;
RT "Phytotoxin production in Aspergillus terreus is regulated by independent
RT environmental signals.";
RL Elife 4:0-0(2015).
RN [13]
RP INDUCTION.
RX PubMed=25852654; DOI=10.3389/fmicb.2015.00184;
RA Gressler M., Hortschansky P., Geib E., Brock M.;
RT "A new high-performance heterologous fungal expression system based on
RT regulatory elements from the Aspergillus terreus terrein gene cluster.";
RL Front. Microbiol. 6:184-184(2015).
RN [14]
RP BIOTECHNOLOGY.
RX PubMed=25592371; DOI=10.3892/or.2015.3719;
RA Zhang F., Mijiti M., Ding W., Song J., Yin Y., Sun W., Li Z.;
RT "(+)-Terrein inhibits human hepatoma Bel-7402 proliferation through cell
RT cycle arrest.";
RL Oncol. Rep. 33:1191-1200(2015).
RN [15]
RP BIOTECHNOLOGY.
RX PubMed=27127118;
RA Shibata A., Ibaragi S., Mandai H., Tsumura T., Kishimoto K., Okui T.,
RA Hassan N.M., Shimo T., Omori K., Hu G.F., Takashiba S., Suga S., Sasaki A.;
RT "Synthetic terrein inhibits progression of head and neck cancer by
RT suppressing angiogenin production.";
RL Anticancer Res. 36:2161-2168(2016).
CC -!- FUNCTION: 6-hydroxymellein synthase; part of the gene cluster that
CC mediates the biosynthesis of terrein, a fungal metabolite with
CC ecological, antimicrobial, antiproliferative, and antioxidative
CC activities (PubMed:24816227). The first step in the pathway is
CC performed by the polyketide synthase terA that produces 4-hydroxy-6-
CC methylpyranon (4-HMP), orsellinic acid (OA), and 2,3-dehydro-6-
CC hydroxymellein (2,3-dehydro-6-HM) by condensing acetyl-CoA with two,
CC three, or four malonyl-CoA units, respectively (PubMed:24816227). 4-HMP
CC and OA are not pathway intermediates, but are rather shunt or side
CC products (PubMed:24816227). 2,3-dehydro-6-HM is further converted to 6-
CC hydroxymellein (6-HM) by the 6-hydroxymellein synthase terB
CC (PubMed:24816227). The monooxygenases terC and terD, the multicopper
CC oxidase terE and the Kelch-like protein terF are then involved in the
CC transformation of 6-HM to terrein (PubMed:24816227). Even if they are
CC co-regulated with the other terrein cluster genes, terH and terI seem
CC to be dispensable for terrein production; whereas one or both of the 2
CC transporters terG and terJ are probably required for efficient
CC secretion of metabolites (PubMed:24816227).
CC {ECO:0000269|PubMed:24816227}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:24816227}.
CC -!- INDUCTION: Expression is induced by methionine (PubMed:26173180).
CC Nitrogen starvation induces expression of terB and promotes terrein
CC production during fruit infection, via regulation by areA and atfA
CC (PubMed:26173180). Iron limitation acts as a third independent signal
CC for terrein cluster induction via the iron response regulator hapX
CC (PubMed:26173180). Finally, expression is under the control of the
CC terrein cluster-specific transcription factor terR (PubMed:25852654).
CC {ECO:0000269|PubMed:25852654, ECO:0000269|PubMed:26173180}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of terrein
CC (PubMed:24816227). {ECO:0000269|PubMed:24816227}.
CC -!- BIOTECHNOLOGY: Terrein shows anticancer activity on various tumors
CC including cervical carcinoma, ovarian cancer, and head and neck cancer
CC (PubMed:23417151, PubMed:25318762, PubMed:27127118, PubMed:25592371).
CC The secondary metabolite acts as angiogenesis inhibitors through the
CC inhibition of angiogenin secretion (PubMed:18776656, PubMed:27127118).
CC Terrein has also anti-inflammatory activity (PubMed:18358890). It shows
CC an alleviative function of age-related inflammation characterized as an
CC anti-oxidant and might therefore be a useful nutraceutical compound for
CC anti-aging (PubMed:26416516). Terrein may enhance osseointegration by
CC decreasing the level of ROS and has a potentially synergistic effect on
CC osteoblast differentiation (PubMed:21104936). Terrein has also been
CC shown to act as a melanogenesis inhibitor (PubMed:15558216,
CC PubMed:15603975, PubMed:19493001). {ECO:0000269|PubMed:15558216,
CC ECO:0000269|PubMed:15603975, ECO:0000269|PubMed:18358890,
CC ECO:0000269|PubMed:18776656, ECO:0000269|PubMed:19493001,
CC ECO:0000269|PubMed:21104936, ECO:0000269|PubMed:23417151,
CC ECO:0000269|PubMed:25318762, ECO:0000269|PubMed:25592371,
CC ECO:0000269|PubMed:26416516, ECO:0000269|PubMed:27127118}.
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DR EMBL; CH476594; EAU38790.1; -; Genomic_DNA.
DR RefSeq; XP_001210230.1; XM_001210230.1.
DR AlphaFoldDB; Q0D1P0; -.
DR SMR; Q0D1P0; -.
DR PRIDE; Q0D1P0; -.
DR EnsemblFungi; EAU38790; EAU38790; ATEG_00144.
DR GeneID; 4354901; -.
DR VEuPathDB; FungiDB:ATEG_00144; -.
DR eggNOG; ENOG502T21R; Eukaryota.
DR HOGENOM; CLU_310148_0_0_1; -.
DR OMA; ATIMEPR; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Reference proteome; Transferase.
FT CHAIN 1..952
FT /note="6-hydroxymellein synthase terB"
FT /id="PRO_0000437591"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 15..284
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 446..621
FT /note="Methyltransferase (MeT) domain"
FT /evidence="ECO:0000255"
FT REGION 847..938
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
SQ SEQUENCE 952 AA; 105041 MW; 7C861ED70AA76908 CRC64;
MKVDMHQAEQ WPSQRLLGSR APQSNDNELS WTSVLNSEED PWLYDQILFG RRTFPVAGYV
AIAGECMRQL SDSKLEFFST KDLSIGSSLV FDPDDKLELH TTLRPQRLDE ENRQWYEIEI
ASRNGGQSTA LCTGLVAREV LDTQILPDLT RHGDSNWPVS PDYWYDMVAD RGIEYGASQR
GLNDISVDFT ENKASATILP ALDTTDSVAH PVFIDHCLQL SMVAACKGQG RLLADLSVVT
SIQHLVVSNN AWSKLRVNSV VTPGRLQNLT CNFSAVNENG LPILSGQCNI TPIPDLERQS
DGKLFSFINW ATDSTFHNLN QSLAPFQSDL DSTVALERLA LLYALRSEDI GAQSQPYSKK
ILKKIGTKRK GRFGLVPDVS PFVGCGPSGR AELIKLLKAQ ISGTELSSLG HALERCLTEN
TPFSGSNRER QLLLDQLHPL IRNSGTLCES LRLLAYKNPK MNVLELGSGR KDSSNLVLKA
LRTQFDEQLY SSYLSASASL DATTGPKESS RTNGHVQPLV FDAEKSIEEQ GLKAGSYDLI
IITDVAALGS NAALGAKSLK RLIRPQGHVL LLEGVPEPEW LLVLKDYLTK ESPEASTGSK
TKSSFEDVSA ALTKNGFVFE DPDNKLTSAP KVFARLKQPV PETSSEITVV GPTYHLPLIR
EVEKTFGDHN IKCVKSTMDD DIPPGRDIMV FVDFDEPYVY NITEAELSKF VKLVSGMKGK
MIWVTPSAQI YCKNPNSSLI LGLMRTMRSE FKKDITTVEL DPKRTMNVSL SKSLLQIYEG
LSRRGKSKDL DPDYEYAIVD GVIKTPRLQW TTAEAEYAHL ASLRAEQDSG PQSCHMAATV
RFRPDCCYLL VGGLGGLGRM ISAWMVENGA RHIIFFSRSA KEGPETTPFF DRLRAQGCTV
TPFVGSVTNL PDVEEAIKQA TAPVAGVIQM SAVMRVRIFA FDPEPLLTGI EG
