NOTM_ASPVE
ID NOTM_ASPVE Reviewed; 454 AA.
AC L7WRZ2;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Notoamide biosynthesis cluster protein M' {ECO:0000303|PubMed:23213353};
GN Name=notM' {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 notM' 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}.
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DR EMBL; JQ708194; AGC83584.1; -; Genomic_DNA.
DR AlphaFoldDB; L7WRZ2; -.
DR VEuPathDB; FungiDB:ASPVEDRAFT_371541; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046873; F:metal ion transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0015693; P:magnesium ion transport; IEA:UniProt.
DR InterPro; IPR045863; CorA_TM1_TM2.
DR InterPro; IPR002523; MgTranspt_CorA/ZnTranspt_ZntB.
DR Pfam; PF01544; CorA; 1.
DR SUPFAM; SSF144083; SSF144083; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..454
FT /note="Notoamide biosynthesis cluster protein M'"
FT /id="PRO_0000448831"
FT TRANSMEM 334..354
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 205..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..221
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 454 AA; 53003 MW; 22ED6EF37D1CDE7E CRC64;
MDYAAERAPP GVQIYMDVGD PDGWRYCGND MNIVERDQSA NFIIFVTSDI NDTDKSFKLR
FQEEFRPVLD ADINGSFDCH YGCSQSRVWP EGSPESVSSP VMFVVSNIAL VSWSCFKIKE
VKTAEDYSWK QPTIHVQWNA ETGSQIVHVF GFNPDQQSVF MDKLPTAAER KCNPFSLHAA
FSRIILQQYD DAFWLLRDLV RHHEKARSKE KKPKRKKSKA EKEHERKIFP LLHDIARHLF
HYQETIEVAE HTLQVMAKEL LNWRHEDGNN IQQNIGTWLE TRRRILHEEK RAHSLKTRSK
SLNDRHQNEI NLRQAFNLVS QDFGRDARSD SNMMTTVAFV SMVYLPGTFV SGLFGTNFFS
FQADPGNTWL TADEFWMYWA VTIPLTLLTL GVWGVWHWWD TYVGWVQKMR DKKAKSTKSD
EKDATADRNP EPFNLRQRIR TATRLNEIQR KETV
