S7ZFL4 · POXK_PENO1

Function

function

Hydroxylase/desaturase; part of the gene cluster that mediates the biosynthesis of oxaleimides, cytotoxic compounds containing an unusual disubstituted succinimide moiety (PubMed:28365998).
The first step of the pathway is provided by the HR-PKS poxF that serves in a new mode of collaborative biosynthesis with the PKS-NRPS poxE, by providing the olefin containing amino acid substrate via the synthesis of an ACP-bound dec-4-enoate (PubMed:28365998).
The cytochrome P450 monooxygenase poxM-catalyzed oxidation at the alpha-position creates the enzyme-bound 2-hydroxydec-4-enoyl-ACP thioester, which may be prone to spontaneous hydrolysis to yield 2-hydroxydec-4-enoic acid due to increased electrophilicity of the carbonyl (PubMed:28365998).
2-hydroxydec-4-enoic acid can then be further oxidized by poxM to yield the alpha-ketoacid 2-oxodec-4-enoicacid, which is reductively aminated by the aminotransferase poxL to yield (S,E)-2-aminodec-4-enoic acid (PubMed:28365998).
The Hybrid PKS-NRPS synthetase poxE then performs condensation between the octaketide product of its PKS modules and the amino group of (S,E)-2-aminodec-4-enoic acid which is activated and incorporated by the adenylation domain (PubMed:28365998).
The resulting aminoacyl product can be cyclized by the Diels-Alderase PoxQ and reductively released by the reductive (R) domain of poxE to yield an aldehyde intermediate (Probable) (PubMed:28365998).
The released aldehyde is then substrate for a Knoevenagel condensation by the hydrolyase poxO followed by an oxidation at the 5-position of the pyrrolidone ring (PubMed:28365998).
The presence of the olefin from the amino acid building block allows for migration of the substituted allyl group to occur (PubMed:28365998).
This allylic transposition reaction takes place in a conjugate addition, semipinacol-like fashion to yield a succinimide intermediate (PubMed:28365998).
Iterative two-electron oxidations of the C7 methyl of the succinimide intermediate to the carboxylic acid can be catalyzed by one of two remaining cytochrome P450 monooxygenasess poxC or poxD to yield oxaleimide A (PubMed:28365998).
Subsequent oxidation yields the maleimide scaffold oxaleimide I (PubMed:28365998).
Both oxaleimide A and oxaleimide I can undergo oxidative modifications in the decalin ring to yield the series of products oxaleimides B to H (PubMed:28365998).

Pathway

Secondary metabolite biosynthesis.

GO annotations

AspectTerm
Molecular Functionoxidoreductase activity

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Hydroxylase/desaturase poxK
  • EC number
  • Alternative names
    • Oxaleimides biosynthesis cluster protein K

Gene names

    • Name
      poxK
    • ORF names
      PDE_04023

Organism names

Accessions

  • Primary accession
    S7ZFL4

Proteomes

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004537761-325Hydroxylase/desaturase poxK

Expression

Induction

Expression is positively regulated by the oxaleimides biosynthesis cluster-specific transcription factor poxB.

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-25Disordered

Sequence similarities

Belongs to the asaB hydroxylase/desaturase family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    325
  • Mass (Da)
    35,598
  • Last updated
    2013-10-16 v1
  • Checksum
    CBD7C75A3ECD9012
MTATATPVPTVASHAQDITLPPPPKGDITTPILFAQDFQKPSTGYMFIKNPPPAGVPYTNIRGEPAMVTVEDLRGKENSVNLDRDSLQVLQGLTDVPRSPEVNWNSVESVEKTFYPAVEAAIKSAIPGAHTVHIFRHGIRHTQNWPVPYNPPAMIAHLDQTGPAAINRVLRHMGPVEGPRLLQGRYRIVHFWTPLNGPVYTCPVAVASSATVKDNDIQIFVSHLGGIGGLDMPLGRPVAKPDASEQYREDFGAPRYADGQRWFYLSGITQDEALLIQIFDSNALQKDSTVQGGRAVHSAFRDPRTPQGAPDRWSIEVSCLVFSDE

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KB644411
EMBL· GenBank· DDBJ
EPS29074.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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