ID   NOTN_ASPVE              Reviewed;         416 AA.
AC   L7WR53;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 1.
DT   25-MAY-2022, entry version 12.
DE   RecName: Full=Notoamide biosynthesis cluster protein N' {ECO:0000303|PubMed:23213353};
DE   Flags: Precursor;
GN   Name=notN' {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 notN' 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   -!- 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}.
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DR   EMBL; JQ708194; AGC83585.1; -; Genomic_DNA.
DR   AlphaFoldDB; L7WR53; -.
DR   VEuPathDB; FungiDB:ASPVEDRAFT_178400; -.
PE   1: Evidence at protein level;
KW   Glycoprotein; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..416
FT                   /note="Notoamide biosynthesis cluster protein N'"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_5003985463"
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   416 AA;  44842 MW;  04FD4C828108B7AE CRC64;
     MRAALLTLAF TALAAAADDA TTTVGFFGGG EWENSNDDDS LPLIPSYTSI GASVVDVNAV
     ETVLAISCLE GAATESCSIN DPWTMTQGIS SFSWYAEYTA FDWNPPVTAT LDYNCAYENY
     TLSATCTYSM SYSGSSDGAE TSTSFSTETS WDSVATYAAL EVTGGLDKFN QPEATETPEG
     GAGFAGPIQA MVTAAPVLAA GLLASHASGA WRKGKILLIK PFKGILPRLA RLEASVKSPN
     PYRNEPLTPN LDIRAPSSGQ CNASLYTRHH PGCFDDDIDS LGQVVLSSQV LGVFFNRLCR
     VEFVCPDAQF ACRECQPVFV DIHCNDVPST KLPCCRGRKQ TNRPCPKNKH ILAWLELCKA
     EAMHRDSKGL KDNAFVKPYV VGELVAEVPR QAEKGRQRAM DNIARSRNCG KGHVRT