NOTO_ASPVE
ID NOTO_ASPVE Reviewed; 462 AA.
AC L7WU90;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 25-MAY-2022, entry version 23.
DE RecName: Full=Notoamide biosynthesis cluster protein O' {ECO:0000303|PubMed:23213353};
DE AltName: Full=UNC93-like protein notO' {ECO:0000305};
GN Name=notO' {ECO:0000303|PubMed:23213353};
OS Aspergillus versicolor.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=46472;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL 35600;
RX PubMed=23213353; DOI=10.1039/c2md20029e;
RA Li S., Anand K., Tran H., Yu F., Finefield J.M., Sunderhaus J.D.,
RA McAfoos T.J., Tsukamoto S., Williams R.M., Sherman D.H.;
RT "Comparative analysis of the biosynthetic systems for fungal
RT bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide,
RT paraherquamide and malbrancheamide pathways.";
RL Med. Chem. Commun. 3:987-996(2012).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=17304611; DOI=10.1002/anie.200604381;
RA Kato H., Yoshida T., Tokue T., Nojiri Y., Hirota H., Ohta T.,
RA Williams R.M., Tsukamoto S.;
RT "Notoamides A-D: prenylated indole alkaloids isolated from a marine-derived
RT fungus, Aspergillus sp.";
RL Angew. Chem. Int. Ed. 46:2254-2256(2007).
RN [3]
RP FUNCTION.
RX PubMed=22660767; DOI=10.1007/s00253-012-4130-0;
RA Yin S., Yu X., Wang Q., Liu X.Q., Li S.M.;
RT "Identification of a brevianamide F reverse prenyltransferase BrePT from
RT Aspergillus versicolor with a broad substrate specificity towards
RT tryptophan-containing cyclic dipeptides.";
RL Appl. Microbiol. Biotechnol. 97:1649-1660(2013).
CC -!- FUNCTION: Part of the gene cluster that mediates the biosynthesis of
CC notoamide, a fungal indole alkaloid that belongs to a family of natural
CC products containing a characteristic bicyclo[2.2.2]diazaoctane core
CC (PubMed:23213353). The first step of notoamide biosynthesis involves
CC coupling of L-proline and L-tryptophan by the bimodular NRPS notE', to
CC produce cyclo-L-tryptophan-L-proline called brevianamide F (Probable).
CC The reverse prenyltransferase notF' then acts as a deoxybrevianamide E
CC synthase and converts brevianamide F to deoxybrevianamide E via reverse
CC prenylation at C-2 of the indole ring leading to the
CC bicyclo[2.2.2]diazaoctane core (PubMed:22660767) (Probable).
CC Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring,
CC likely catalyzed by the cytochrome P450 monooxygenase notG', to yield
CC 6-hydroxy-deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E
CC is a specific substrate of the prenyltransferase notC' for normal
CC prenylation at C-7 to produce 6-hydroxy-7-prenyl-deoxybrevianamide,
CC also called notoamide S (Probable). As the proposed pivotal branching
CC point in notoamide biosynthesis, notoamide S can be diverted to
CC notoamide E through an oxidative pyran ring closure putatively
CC catalyzed by either notH' cytochrome P450 monooxygenase or the notD'
CC FAD-linked oxidoreductase (Probable). This step would be followed by an
CC indole 2,3-epoxidation-initiated pinacol-like rearrangement catalyzed
CC by the notB' FAD-dependent monooxygenase leading to the formation of
CC notoamide C and notoamide D (Probable). On the other hand notoamide S
CC is converted to notoamide T by notH' (or notD'), a bifunctional oxidase
CC that also functions as the intramolecular Diels-Alderase responsible
CC for generation of (-)-notoamide T (Probable). To generate antipodal
CC (+)-notoaminide T, notH (or notD) in Aspergillus strain MF297-2 is
CC expected to catalyze a Diels-Alder reaction leading to the opposite
CC stereochemistry (Probable). The remaining oxidoreductase notD' (or
CC notH') likely catalyzes the oxidative pyran ring formation to yield
CC (-)-stephacidin A (Probable). The FAD-dependent monooxygenase notI' is
CC highly similar to notB' and is predicted to catalyze a similar
CC conversion from (-)-stephacidin A to (+)-notoamide B via the 2,3-
CC epoxidation of (-)-stephacidin A followed by a pinacol-type
CC rearrangement (Probable). Finally, it remains unclear which enzyme
CC could be responsible for the final hydroxylation steps leading to
CC notoamide A and sclerotiamide (Probable). The fonction of notO' in the
CC notoamide biosynthesis has not been determined yet (Probable).
CC {ECO:0000269|PubMed:22660767, ECO:0000269|PubMed:23213353,
CC ECO:0000305|PubMed:23213353}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Notoamides have been shown to exhibit antitumoral
CC activities (PubMed:17304611). Notoamides A-C show moderate cytotoxicity
CC against HeLa and L1210 cells with IC(50) values in the range of 22-52
CC mg/ml, but the IC(50) value of notoamide D is greater than 100 mg/ml
CC (PubMed:17304611). Moreover, notoamide C induces G2/M-cell cycle arrest
CC at a concentration of 6.3 mg/ml (PubMed:17304611).
CC {ECO:0000269|PubMed:17304611}.
CC -!- SIMILARITY: Belongs to the unc-93 family. {ECO:0000305}.
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DR EMBL; JQ708194; AGC83586.1; -; Genomic_DNA.
DR AlphaFoldDB; L7WU90; -.
DR SMR; L7WU90; -.
DR VEuPathDB; FungiDB:ASPVEDRAFT_33850; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..462
FT /note="Notoamide biosynthesis cluster protein O'"
FT /id="PRO_0000448824"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..363
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 443..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 462 AA; 50806 MW; 2C87ECA19B069202 CRC64;
MNTPTPTQRT WYRTTIFNVS VVAVCAFIAP GLWAAMNGLG GAGSADPYYV NAANAVIFCL
QVVVCVFGSS LIAKIGLKWA FALGMVGFPI YASSVYCNVK YNNSWYIMLA CVIDGICSGI
FWLTEGAIVL AYPEKHRRGK YLAYWLASRI MGQMIGGAVT LGVNAGNQEE GHISVQTYLV
FISIQAIGPF VAATLSPPEK VQRSDQSKVK INLPAGLKAE LHAMWKLLGR TEILLLLPMM
FQSVFSEAFF STYNATYFTV RSRALSSLVA STCVIISNFL LGFFLDWRRL SVNTRAMAAF
IIIYAFELSL YVYAMVVNKE YERQEPRPLF DWTDDGFGRA VCVYILMLVG FNLMYDYLYW
LIGTVNRDGG DIIRLSAVVR GVESAGQAIS YGINSVDSFL LSSAVAVNLS FFAACIVPSA
FVIYRVGVVN GVKVHHIQQD ETLQTSGEGS HDIMDANGKS DD
