E1ACQ5 · NOTJ_ASPSM
- ProteinNotoamide biosynthesis cluster protein J
- GenenotJ
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids370 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score2/5
Function
function
Part of the gene cluster that mediates the biosynthesis of notoamide, a fungal indole alkaloid that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core (PubMed:20722388).
The first step of notoamide biosynthesis involves coupling of L-proline and L-tryptophan by the bimodular NRPS notE, to produce cyclo-L-tryptophan-L-proline called brevianamide F (PubMed:20722388).
The reverse prenyltransferase notF then acts as a deoxybrevianamide E synthase and converts brevianamide F to deoxybrevianamide E via reverse prenylation at C-2 of the indole ring leading to the bicyclo[2.2.2]diazaoctane core (PubMed:20722388).
Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring, likely catalyzed by the cytochrome P450 monooxygenase notG, to yield 6-hydroxy-deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E is a specific substrate of the prenyltransferase notC for normal prenylation at C-7 to produce 6-hydroxy-7-prenyl-deoxybrevianamide, also called notoamide S (PubMed:20722388).
As the proposed pivotal branching point in notoamide biosynthesis, notoamide S can be diverted to notoamide E through an oxidative pyran ring closure putatively catalyzed by either notH cytochrome P450 monooxygenase or the notD FAD-linked oxidoreductase (Probable). This step would be followed by an indole 2,3-epoxidation-initiated pinacol-like rearrangement catalyzed by the notB FAD-dependent monooxygenase leading to the formation of notoamide C and notoamide D (PubMed:22188465).
On the other hand notoamide S is converted to notoamide T by notH (or notD), a bifunctional oxidase that also functions as the intramolecular Diels-Alderase responsible for generation of +-notoamide T (Probable). To generate antipodal --notoaminide T, notH' (or notD') in Aspergillus versicolor is expected to catalyze a Diels-Alder reaction leading to the opposite stereochemistry (Probable). The remaining oxidoreductase notD (or notH) likely catalyzes the oxidative pyran ring formation to yield +-stephacidin A (Probable). The FAD-dependent monooxygenase notI is highly similar to notB and is predicted to catalyze a similar conversion from +-stephacidin A to --notoamide B via the 2,3-epoxidation of +-stephacidin A followed by a pinacol-type rearrangement (Probable). Finally, it remains unclear which enzyme could be responsible for the final hydroxylation steps leading to notoamide A and sclerotiamide (Probable). The function of notJ in the notoamide biosynthesis has not been determined yet (Probable).
The first step of notoamide biosynthesis involves coupling of L-proline and L-tryptophan by the bimodular NRPS notE, to produce cyclo-L-tryptophan-L-proline called brevianamide F (PubMed:20722388).
The reverse prenyltransferase notF then acts as a deoxybrevianamide E synthase and converts brevianamide F to deoxybrevianamide E via reverse prenylation at C-2 of the indole ring leading to the bicyclo[2.2.2]diazaoctane core (PubMed:20722388).
Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring, likely catalyzed by the cytochrome P450 monooxygenase notG, to yield 6-hydroxy-deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E is a specific substrate of the prenyltransferase notC for normal prenylation at C-7 to produce 6-hydroxy-7-prenyl-deoxybrevianamide, also called notoamide S (PubMed:20722388).
As the proposed pivotal branching point in notoamide biosynthesis, notoamide S can be diverted to notoamide E through an oxidative pyran ring closure putatively catalyzed by either notH cytochrome P450 monooxygenase or the notD FAD-linked oxidoreductase (Probable). This step would be followed by an indole 2,3-epoxidation-initiated pinacol-like rearrangement catalyzed by the notB FAD-dependent monooxygenase leading to the formation of notoamide C and notoamide D (PubMed:22188465).
On the other hand notoamide S is converted to notoamide T by notH (or notD), a bifunctional oxidase that also functions as the intramolecular Diels-Alderase responsible for generation of +-notoamide T (Probable). To generate antipodal --notoaminide T, notH' (or notD') in Aspergillus versicolor is expected to catalyze a Diels-Alder reaction leading to the opposite stereochemistry (Probable). The remaining oxidoreductase notD (or notH) likely catalyzes the oxidative pyran ring formation to yield +-stephacidin A (Probable). The FAD-dependent monooxygenase notI is highly similar to notB and is predicted to catalyze a similar conversion from +-stephacidin A to --notoamide B via the 2,3-epoxidation of +-stephacidin A followed by a pinacol-type rearrangement (Probable). Finally, it remains unclear which enzyme could be responsible for the final hydroxylation steps leading to notoamide A and sclerotiamide (Probable). The function of notJ in the notoamide biosynthesis has not been determined yet (Probable).
Biotechnology
Notoamides have been shown to exhibit antitumoral activities (PubMed:17304611).
Notoamides A-C show moderate cytotoxicity against HeLa and L1210 cells with IC50 values in the range of 22-52 mg/ml, but the IC50 value of notoamide D is greater than 100 mg/ml (PubMed:17304611).
Moreover, notoamide C induces G2/M-cell cycle arrest at a concentration of 6.3 mg/ml (PubMed:17304611).
Notoamides A-C show moderate cytotoxicity against HeLa and L1210 cells with IC50 values in the range of 22-52 mg/ml, but the IC50 value of notoamide D is greater than 100 mg/ml (PubMed:17304611).
Moreover, notoamide C induces G2/M-cell cycle arrest at a concentration of 6.3 mg/ml (PubMed:17304611).
Names & Taxonomy
Protein names
- Recommended nameNotoamide biosynthesis cluster protein J
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus
Accessions
- Primary accessionE1ACQ5
Phenotypes & Variants
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-22 | |||||
Sequence: MRIMSIMLHLLATILLSSAVSA | ||||||
Chain | PRO_5003143467 | 23-370 | Notoamide biosynthesis cluster protein J | |||
Sequence: QNANAASTRRLIGEDRESGRRWGVAATDLGIPYDQHNGEIGFLFGDTVSTKWVQEAKDLRSPVMLRSGIHPGEDGGIVFESAAGVDGDGLAPRLFYNGDRGDDGTGTGTWEFTVLPNDGISFPETGEHIISYLSIMNFTTPWTPNYSGLAYSTDGNTFTRLPTKWLNNDNNTDPFQMWTMQRDGDWVYVFTVRSAPQYGPLMLQRVPWDKMTNKTEYQGWGWNGEDWGWQRPCSPILDGYFGEPSVRRLHDGTWAMVYLNASTSTPHIVSRSAKDPTGPWSEEKVQVNQEGDGSLLYGGFIHPWSTSKGNQLYLMVSNWTSTSNLSQTTEAVADYEGTVSVSQFTGTL | ||||||
Glycosylation | 159 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 167 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 192 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 235 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 282 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 340 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 346 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
PTM databases
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length370
- Mass (Da)41,041
- Last updated2010-11-02 v1
- Checksum1F3BF35481DB7179