E1ACQ5 · NOTJ_ASPSM

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).

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).

Names & Taxonomy

Protein names

  • Recommended name
    Notoamide biosynthesis cluster protein J

Gene names

    • Name
      notJ

Organism names

  • Taxonomic identifier
  • Strain
    • MF297-2
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus

Accessions

  • Primary accession
    E1ACQ5

Phenotypes & Variants

PTM/Processing

Features

Showing features for signal, chain, glycosylation.

TypeIDPosition(s)Description
Signal1-22
ChainPRO_500314346723-370Notoamide biosynthesis cluster protein J
Glycosylation159N-linked (GlcNAc...) asparagine
Glycosylation167N-linked (GlcNAc...) asparagine
Glycosylation192N-linked (GlcNAc...) asparagine
Glycosylation235N-linked (GlcNAc...) asparagine
Glycosylation282N-linked (GlcNAc...) asparagine
Glycosylation340N-linked (GlcNAc...) asparagine
Glycosylation346N-linked (GlcNAc...) asparagine

Keywords

PTM databases

Structure

Family & Domains

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    370
  • Mass (Da)
    41,041
  • Last updated
    2010-11-02 v1
  • Checksum
    1F3BF35481DB7179
MRIMSIMLHLLATILLSSAVSAQNANAASTRRLIGEDRESGRRWGVAATDLGIPYDQHNGEIGFLFGDTVSTKWVQEAKDLRSPVMLRSGIHPGEDGGIVFESAAGVDGDGLAPRLFYNGDRGDDGTGTGTWEFTVLPNDGISFPETGEHIISYLSIMNFTTPWTPNYSGLAYSTDGNTFTRLPTKWLNNDNNTDPFQMWTMQRDGDWVYVFTVRSAPQYGPLMLQRVPWDKMTNKTEYQGWGWNGEDWGWQRPCSPILDGYFGEPSVRRLHDGTWAMVYLNASTSTPHIVSRSAKDPTGPWSEEKVQVNQEGDGSLLYGGFIHPWSTSKGNQLYLMVSNWTSTSNLSQTTEAVADYEGTVSVSQFTGTL

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
HM622670
EMBL· GenBank· DDBJ
ADM34143.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp