A0A3G1DJE9 · MFM3_PHOSM

Function

function

NADP-dependent dehydrogenase; part of the gene cluster that mediates the biosynthesis of squalestatin S1 (SQS1, also known as zaragozic acid A), a heavily oxidized fungal polyketide that offers potent cholesterol lowering activity by targeting squalene synthase (SS) (PubMed:27056201).
SQS1 is composed of a 2,8-dioxobicyclic[3.2.1]octane-3,4,5-tricarboxyclic acid core that is connected to two lipophilic polyketide arms (PubMed:27056201).
These initial steps feature the priming of an unusual benzoic acid starter unit onto the highly reducing polyketide synthase pks2, followed by oxaloacetate extension and product release to generate a tricarboxylic acid containing product (By similarity).
The phenylalanine ammonia lyase (PAL) M7 and the acyl-CoA ligase M9 are involved in transforming phenylalanine into benzoyl-CoA (By similarity).
The citrate synthase-like protein R3 is involved in connecting the C-alpha-carbons of the hexaketide chain and oxaloacetate to afford the tricarboxylic acid unit (By similarity).
The potential hydrolytic enzymes, M8 and M10, are in close proximity to pks2 and may participate in product release (By similarity).
On the other side, the tetraketide arm is synthesized by a the squalestatin tetraketide synthase pks1 and enzymatically esterified to the core in the last biosynthetic step, by the acetyltransferase M4 (PubMed:11251290, PubMed:15489970, PubMed:28106181).
The biosynthesis of the tetraketide must involve 3 rounds of chain extension (PubMed:11251290, PubMed:15489970, PubMed:28106181).
After the first and second rounds methyl-transfer occurs, and in all rounds of extension the ketoreductase and dehydratase are active (PubMed:11251290, PubMed:15489970, PubMed:28106181).
The enoyl reductase and C-MeT of pks1 are not active in the final round of extension (PubMed:11251290, PubMed:15489970, PubMed:28106181).
The acetyltransferase M4 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins (Probable). The biosynthesis of SQS1 requires several oxidative steps likely performed by oxidoreductases M1, R1 and R2 (Probable). Finally, in support of the identification of the cluster as being responsible for SQS1 production, the cluster contains a gene encoding a putative squalene synthase (SS) R6, suggesting a likely mechanism for self-resistance (Probable)

Pathway

Secondary metabolite biosynthesis.

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site49NADP+ (UniProtKB | ChEBI)
Binding site51NADP+ (UniProtKB | ChEBI)
Binding site93NADP+ (UniProtKB | ChEBI)
Active site206Proton acceptor
Binding site206NADP+ (UniProtKB | ChEBI)
Active site210Lowers pKa of active site Tyr
Binding site210NADP+ (UniProtKB | ChEBI)
Binding site240NADP+ (UniProtKB | ChEBI)
Binding site244NADP+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Molecular Functionoxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    NADP-dependent dehydrogenase M3
  • EC number
  • Alternative names
    • Squalestatin S1 biosynthesis cluster protein M3

Gene names

    • Name
      M3

Organism names

Accessions

  • Primary accession
    A0A3G1DJE9

Subcellular Location

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004478331-339NADP-dependent dehydrogenase M3

Expression

Induction

Expression is induced on squalestatin S1-producing YMG medium.

Interaction

Subunit

Homodimer.

Family & Domains

Sequence similarities

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    339
  • Mass (Da)
    36,438
  • Last updated
    2019-02-13 v1
  • Checksum
    AEBE2CD949937785
MAATNDPELTRRKQRQEDFLRGTSKINFDDHIDHCVLSGKTAIVTGGASGIGHGIAQALSSNGCKVAVLDLSGPLEAGTDESNIDSPKLFECDVSSWESLLAAFQEVLIWSGNSLDIVVLSAGVRSHNIKDLILERPAGSTSTPVKPPSSVFDVNLLGTYYSAYLALWYFTNLEAKRDEAEFNWKPQLLFIGSLASYVEQPLSADYCASKHGVRGLWKSVRSHSALFGDCQTNLLAPTFIDNRQGSTKSRGDGALISLTNDVKLGEVSDVVAGALRCLCDRNIEGRALCCVKGEQSSPGSNNFDLCDNLIDFNAGKSVLDSFRNGVVGRLGTQNTTGPQ

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KU946987
EMBL· GenBank· DDBJ
AMY15060.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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