L0E301 · PHQJ_PENFE

  • Protein
    Prenyltransferase phqJ
  • Gene
    phqJ
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Inferred from homology
  • Annotation score
    3/5

Function

function

Prenyltransferase; part of the gene cluster that mediates the biosynthesis of paraherquamide, a fungal indole alkaloid that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core (PubMed:23213353).
The first steps in the biosynthesis of paraherquamide is the production of the beta-methyl-proline precursor from L-isoleucine (Probable). They require oxidation of a terminally hydroxylated L-isoleucine to the corresponding aldehyde by enzymes which have still to be identified (Probable). Spontaneous cyclization and dehydration would yield the 4-methyl pyrolline-5-carboxylic acid, which is then reduced by the pyrroline-5-carboxylate reductase phqD leading to the beta-methyl-proline precursor (Probable). The next step of paraherquamide biosynthesis involves coupling of beta-methyl-proline and L-tryptophan by the bimodular NRPS phqB, to produce a monooxopiperazine intermediate (Probable). The reductase (R) domain of phqB utilizes NADPH for hydride transfer to reduce the thioester bond of the T domain-tethered linear dipeptide to a hemithioaminal intermediate, which spontaneously cleaves the C-S bond to release the aldehyde product (PubMed:31548667).
This compound undergoes spontaneous cyclization and dehydration to give a dienamine which is reverse prenylated at C-2 by the reverse prenyltransferase phqJ (Probable). The other prenyltransferase present in the cluster, phqI may be a redundant gene in the pathway (Probable). During biosynthetic assembly, the key step to produce the polycyclic core is catalyzed by the bifunctional reductase and intramolecular [4+2] Diels-Alderase, phqE, resulting in formation of the [2.2.2] diazaoctane intermediate preparaherquamide (PubMed:31548667).
Following formation of preparaherquamide, an indole 2,3-epoxidation-initiated pinacol-like rearrangement is catalyzed by the phqK FAD-dependent monooxygenase (Probable). The prenyltransferase phqA, the cytochrome P450 monooxygenase phqL, and the FAD-linked oxidoreductase phqH (or the cytochrome P450 monooxygenase phqM), are proposed to be involved in the formation of the pyran ring (Probable). The FAD-dependent monooxygenase phqK is likely responsible for generation of the spiro-oxindole, and the N-methylation is likely mediated by the phqN methyltransferase leading to the isolable natural product paraherquamide F (Probable). However, the order of these biosynthetic steps has still to be determined (Probable). In late-stage paraherquamide biosynthesis, the third P450 monooxygenase, phqO, is probably responsible for the C-14 hydroxylation, transforming paraherquamide F to paraherquamide G, and paraherquamide E to the final product paraherquamide A (Probable). The expansion from the 6-membered ring pyran (in paraherquamides F and G) to the 7-membered dioxepin ring (in paraherquamides A and E) represents a poorly understood but intriguing process that probably involves the 2-oxoglutarate-dependent dioxygenase phqC (Probable). Finally, the remaining members of the paraherquamide cluster, including phqI as well as phqM (or phqH), do not have a clearly prescribed role and appear to be redundant (Probable)

Pathway

Alkaloid biosynthesis.

Features

Showing features for binding site, site.

TypeIDPosition(s)Description
Binding site99brevianamide F (UniProtKB | ChEBI)
Binding site113dimethylallyl diphosphate (UniProtKB | ChEBI)
Site115Required for regioselectivity
Binding site200dimethylallyl diphosphate (UniProtKB | ChEBI)
Binding site202dimethylallyl diphosphate (UniProtKB | ChEBI)
Binding site204brevianamide F (UniProtKB | ChEBI)
Binding site269dimethylallyl diphosphate (UniProtKB | ChEBI)
Binding site271dimethylallyl diphosphate (UniProtKB | ChEBI)
Binding site340dimethylallyl diphosphate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Molecular Functionprenyltransferase activity
Biological Processalkaloid metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Prenyltransferase phqJ
  • EC number
  • Alternative names
    • Paraherquamide biosynthesis cluster protein J

Gene names

    • Name
      phqJ

Organism names

  • Taxonomic identifier
  • Strain
    • ATCC 20841 / MF5123
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Penicillium

Accessions

  • Primary accession
    L0E301

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004488651-406Prenyltransferase phqJ

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-23Disordered

Sequence similarities

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    406
  • Mass (Da)
    45,549
  • Last updated
    2013-03-06 v1
  • Checksum
    73C69D0FBC4B9BFC
MTVSTESNFPHGASTQKPQSAEPEIYSSLTKSLDFSNDAEEKWWTRTAPLLSRILDSAGYTLPQQCQFLTLFNTLMIPNFGPHPHIWHSSITHSGLPVEFSVNYQPGKQPTVRIGFEPASSISGTARDPYNMVTVLNVLNKMSRLNFKGFDPSLFHTLISSLALSKNESDLLQGAKLEGSKFKTQAAFGLDLKGDAVTVKTYLYPALKCKVSGLAFSELLEAALAKHQNAHDFSRVLPLVQSYMEEGQCYNQYSFVGFDCVDSSKSRLKIYGALLDISWKKVEEVWTLGARLVNSETNKEGLRYMRALWEYLTPGKERRPVGIWNYELLPGSEEPMPKFYVDMNGENDFQNALGITKFLHHIGLTTTAEGLISKIQEYLYGVPHYPLSQTHVLFANQGPMQPRCEP

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
JQ708195
EMBL· GenBank· DDBJ
AGA37277.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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