ID   NOTJ_ASPSM              Reviewed;         370 AA.
AC   E1ACQ5;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 1.
DT   25-MAY-2022, entry version 16.
DE   RecName: Full=Notoamide biosynthesis cluster protein J {ECO:0000303|PubMed:20722388};
DE   Flags: Precursor;
GN   Name=notJ {ECO:0000303|PubMed:20722388};
OS   Aspergillus sp. (strain MF297-2).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=877550;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=MF297-2;
RX   PubMed=20722388; DOI=10.1021/ja1049302;
RA   Ding Y., de Wet J.R., Cavalcoli J., Li S., Greshock T.J., Miller K.A.,
RA   Finefield J.M., Sunderhaus J.D., McAfoos T.J., Tsukamoto S., Williams R.M.,
RA   Sherman D.H.;
RT   "Genome-based characterization of two prenylation steps in the assembly of
RT   the stephacidin and notoamide anticancer agents in a marine-derived
RT   Aspergillus sp.";
RL   J. Am. Chem. Soc. 132:12733-12740(2010).
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=22188465; DOI=10.1021/ja2093212;
RA   Li S., Finefield J.M., Sunderhaus J.D., McAfoos T.J., Williams R.M.,
RA   Sherman D.H.;
RT   "Biochemical characterization of NotB as an FAD-dependent oxidase in the
RT   biosynthesis of notoamide indole alkaloids.";
RL   J. Am. Chem. Soc. 134:788-791(2012).
RN   [4]
RP   FUNCTION.
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).
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:20722388). 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
CC       (PubMed:20722388). The reverse prenyltransferase notF then acts as a
CC       deoxybrevianamide E synthase and converts brevianamide F to
CC       deoxybrevianamide E via reverse prenylation at C-2 of the indole ring
CC       leading to the bicyclo[2.2.2]diazaoctane core (PubMed:20722388).
CC       Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring,
CC       likely catalyzed by the cytochrome P450 monooxygenase notG, to yield 6-
CC       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 (PubMed:20722388). As the proposed pivotal
CC       branching point in notoamide biosynthesis, notoamide S can be diverted
CC       to notoamide E through an oxidative pyran ring closure putatively
CC       catalyzed by either notH cytochrome P450 monooxygenase or the notD FAD-
CC       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 (PubMed:22188465). On the other hand
CC       notoamide S is converted to notoamide T by notH (or notD), a
CC       bifunctional oxidase that also functions as the intramolecular Diels-
CC       Alderase responsible for generation of (+)-notoamide T (Probable). To
CC       generate antipodal (-)-notoaminide T, notH' (or notD') in Aspergillus
CC       versicolor is expected to catalyze a Diels-Alder reaction leading to
CC       the opposite stereochemistry (Probable). The remaining oxidoreductase
CC       notD (or notH) likely catalyzes the oxidative pyran ring formation to
CC       yield (+)-stephacidin A (Probable). The FAD-dependent monooxygenase
CC       notI is 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 notJ in the
CC       notoamide biosynthesis has not been determined yet (Probable).
CC       {ECO:0000269|PubMed:20722388, ECO:0000269|PubMed:22188465,
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; HM622670; ADM34143.1; -; Genomic_DNA.
DR   AlphaFoldDB; E1ACQ5; -.
DR   InterPro; IPR025442; DUF4185.
DR   InterPro; IPR023296; Glyco_hydro_beta-prop_sf.
DR   Pfam; PF13810; DUF4185; 1.
DR   SUPFAM; SSF75005; SSF75005; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..370
FT                   /note="Notoamide biosynthesis cluster protein J"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_5003143467"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        282
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        346
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   370 AA;  41041 MW;  1F3BF35481DB7179 CRC64;
     MRIMSIMLHL LATILLSSAV SAQNANAAST RRLIGEDRES GRRWGVAATD LGIPYDQHNG
     EIGFLFGDTV STKWVQEAKD LRSPVMLRSG IHPGEDGGIV FESAAGVDGD GLAPRLFYNG
     DRGDDGTGTG TWEFTVLPND GISFPETGEH IISYLSIMNF TTPWTPNYSG LAYSTDGNTF
     TRLPTKWLNN DNNTDPFQMW TMQRDGDWVY VFTVRSAPQY GPLMLQRVPW DKMTNKTEYQ
     GWGWNGEDWG WQRPCSPILD GYFGEPSVRR LHDGTWAMVY LNASTSTPHI VSRSAKDPTG
     PWSEEKVQVN QEGDGSLLYG GFIHPWSTSK GNQLYLMVSN WTSTSNLSQT TEAVADYEGT
     VSVSQFTGTL