L0E301 · PHQJ_PENFE
- ProteinPrenyltransferase phqJ
- GenephqJ
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids406 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
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)
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 99 | brevianamide F (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 113 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Site | 115 | Required for regioselectivity | ||||
Sequence: G | ||||||
Binding site | 200 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 202 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 204 | brevianamide F (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 269 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 271 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 340 | dimethylallyl diphosphate (UniProtKB | ChEBI) | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | prenyltransferase activity | |
Biological Process | alkaloid metabolic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePrenyltransferase phqJ
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Penicillium
Accessions
- Primary accessionL0E301
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000448865 | 1-406 | Prenyltransferase phqJ | |||
Sequence: MTVSTESNFPHGASTQKPQSAEPEIYSSLTKSLDFSNDAEEKWWTRTAPLLSRILDSAGYTLPQQCQFLTLFNTLMIPNFGPHPHIWHSSITHSGLPVEFSVNYQPGKQPTVRIGFEPASSISGTARDPYNMVTVLNVLNKMSRLNFKGFDPSLFHTLISSLALSKNESDLLQGAKLEGSKFKTQAAFGLDLKGDAVTVKTYLYPALKCKVSGLAFSELLEAALAKHQNAHDFSRVLPLVQSYMEEGQCYNQYSFVGFDCVDSSKSRLKIYGALLDISWKKVEEVWTLGARLVNSETNKEGLRYMRALWEYLTPGKERRPVGIWNYELLPGSEEPMPKFYVDMNGENDFQNALGITKFLHHIGLTTTAEGLISKIQEYLYGVPHYPLSQTHVLFANQGPMQPRCEP |
Structure
Sequence
- Sequence statusComplete
- Length406
- Mass (Da)45,549
- Last updated2013-03-06 v1
- Checksum73C69D0FBC4B9BFC