ID   NOTR_ASPVE              Reviewed;         172 AA.
AC   L7WRZ7;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 1.
DT   03-AUG-2022, entry version 17.
DE   RecName: Full=ATP-dependent kinase-like protein notR' {ECO:0000303|PubMed:23213353};
DE            EC=2.7.1.- {ECO:0000305};
DE   AltName: Full=Notoamide biosynthesis cluster protein R' {ECO:0000303|PubMed:23213353};
GN   Name=notR' {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: ATP-dependent kinase-like protein; part of the gene cluster
CC       that mediates the biosynthesis of notoamide, a fungal indole alkaloid
CC       that belongs to a family of natural products containing a
CC       characteristic bicyclo[2.2.2]diazaoctane core (PubMed:23213353). The
CC       first step of notoamide biosynthesis involves coupling of L-proline and
CC       L-tryptophan by the bimodular NRPS notE', to produce cyclo-L-
CC       tryptophan-L-proline called brevianamide F (Probable). The reverse
CC       prenyltransferase notF' then acts as a deoxybrevianamide E synthase and
CC       converts brevianamide F to deoxybrevianamide E via reverse prenylation
CC       at C-2 of the indole ring leading to the bicyclo[2.2.2]diazaoctane core
CC       (PubMed:22660767) (Probable). Deoxybrevianamide E is further
CC       hydroxylated at C-6 of the indole ring, likely catalyzed by the
CC       cytochrome P450 monooxygenase notG', to yield 6-hydroxy-
CC       deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E is a
CC       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 notQ' 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}.
CC   -!- SIMILARITY: Belongs to the YFH7 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; JQ708194; AGC83589.1; -; Genomic_DNA.
DR   AlphaFoldDB; L7WRZ7; -.
DR   SMR; L7WRZ7; -.
DR   VEuPathDB; FungiDB:ASPVEDRAFT_76489; -.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   SUPFAM; SSF52540; SSF52540; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Kinase; Nucleotide-binding; Transferase.
FT   CHAIN           1..172
FT                   /note="ATP-dependent kinase-like protein notR'"
FT                   /id="PRO_0000448830"
SQ   SEQUENCE   172 AA;  19243 MW;  F24F1ED1B836B486 CRC64;
     MDGYHLPRAQ LAAMPDPATA IYRRGAEFTF DGEGFYRLVQ RLRERLTAAS PTVFAPSFDH
     AIKDPVPDDV AISPGSRVII LEGLYLSLNR EPWSSAAALM DESWFVGVDR EIARARLVKR
     HVTSGIVPDT AAAEHRILST DFLNADDIVK NRLPVQEMVP GNWRELSQDR LD