PHQA_PENFE
ID PHQA_PENFE Reviewed; 405 AA.
AC L0E4G3;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Prenyltransferase phqA {ECO:0000303|PubMed:23213353};
DE EC=2.5.1.- {ECO:0000305|PubMed:23213353};
DE AltName: Full=Paraherquamide biosynthesis cluster protein A {ECO:0000303|PubMed:23213353};
GN Name=phqA {ECO:0000303|PubMed:23213353};
OS Penicillium fellutanum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=70095;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=ATCC 20841 / MF5123;
RX PubMed=23213353; DOI=10.1039/c2md20029e;
RA Li S., Anand K., Tran H., Yu F., Finefield J.M., Sunderhaus J.D.,
RA McAfoos T.J., Tsukamoto S., Williams R.M., Sherman D.H.;
RT "Comparative analysis of the biosynthetic systems for fungal
RT bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide,
RT paraherquamide and malbrancheamide pathways.";
RL Med. Chem. Commun. 3:987-996(2012).
RN [2]
RP FUNCTION.
RX PubMed=31548667; DOI=10.1038/s41557-019-0326-6;
RA Dan Q., Newmister S.A., Klas K.R., Fraley A.E., McAfoos T.J., Somoza A.D.,
RA Sunderhaus J.D., Ye Y., Shende V.V., Yu F., Sanders J.N., Brown W.C.,
RA Zhao L., Paton R.S., Houk K.N., Smith J.L., Sherman D.H., Williams R.M.;
RT "Fungal indole alkaloid biogenesis through evolution of a bifunctional
RT reductase/Diels-Alderase.";
RL Nat. Chem. 11:972-980(2019).
CC -!- FUNCTION: Prenyltransferase; part of the gene cluster that mediates the
CC biosynthesis of paraherquamide, a fungal indole alkaloid that belongs
CC to a family of natural products containing a characteristic
CC bicyclo[2.2.2]diazaoctane core (PubMed:23213353). The first steps in
CC the biosynthesis of paraherquamide is the production of the beta-
CC methyl-proline precursor from L-isoleucine (Probable). They require
CC oxidation of a terminally hydroxylated L-isoleucine to the
CC corresponding aldehyde by enzymes which have still to be identified
CC (Probable). Spontaneous cyclization and dehydration would yield the 4-
CC methyl pyrolline-5-carboxylic acid, which is then reduced by the
CC pyrroline-5-carboxylate reductase phqD leading to the beta-methyl-
CC proline precursor (Probable). The next step of paraherquamide
CC biosynthesis involves coupling of beta-methyl-proline and L-tryptophan
CC by the bimodular NRPS phqB, to produce a monooxopiperazine intermediate
CC (Probable). The reductase (R) domain of phqB utilizes NADPH for hydride
CC transfer to reduce the thioester bond of the T domain-tethered linear
CC dipeptide to a hemithioaminal intermediate, which spontaneously cleaves
CC the C-S bond to release the aldehyde product (PubMed:31548667). This
CC compound undergoes spontaneous cyclization and dehydration to give a
CC dienamine which is reverse prenylated at C-2 by the reverse
CC prenyltransferase phqJ (Probable). The other prenyltransferase present
CC in the cluster, phqI may be a redundant gene in the pathway (Probable).
CC During biosynthetic assembly, the key step to produce the polycyclic
CC core is catalyzed by the bifunctional reductase and intramolecular
CC [4+2] Diels-Alderase, phqE, resulting in formation of the [2.2.2]
CC diazaoctane intermediate preparaherquamide (PubMed:31548667). Following
CC formation of preparaherquamide, an indole 2,3-epoxidation-initiated
CC pinacol-like rearrangement is catalyzed by the phqK FAD-dependent
CC monooxygenase (Probable). The prenyltransferase phqA, the cytochrome
CC P450 monooxygenase phqL, and the FAD-linked oxidoreductase phqH (or the
CC cytochrome P450 monooxygenase phqM), are proposed to be involved in the
CC formation of the pyran ring (Probable). The FAD-dependent monooxygenase
CC phqK is likely responsible for generation of the spiro-oxindole, and
CC the N-methylation is likely mediated by the phqN methyltransferase
CC leading to the isolable natural product paraherquamide F (Probable).
CC However, the order of these biosynthetic steps has still to be
CC determined (Probable). In late-stage paraherquamide biosynthesis, the
CC third P450 monooxygenase, phqO, is probably responsible for the C-14
CC hydroxylation, transforming paraherquamide F to paraherquamide G, and
CC paraherquamide E to the final product paraherquamide A (Probable). The
CC expansion from the 6-membered ring pyran (in paraherquamides F and G)
CC to the 7-membered dioxepin ring (in paraherquamides A and E) represents
CC a poorly understood but intriguing process that probably involves the
CC 2-oxoglutarate-dependent dioxygenase phqC (Probable). Finally, the
CC remaining members of the paraherquamide cluster, including phqI as well
CC as phqM (or phqH), do not have a clearly prescribed role and appear to
CC be redundant (Probable). {ECO:0000269|PubMed:23213353,
CC ECO:0000269|PubMed:31548667, ECO:0000305|PubMed:23213353}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:23213353}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; JQ708195; AGA37268.1; -; Genomic_DNA.
DR AlphaFoldDB; L0E4G3; -.
DR SMR; L0E4G3; -.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
PE 3: Inferred from homology;
KW Alkaloid metabolism; Prenyltransferase; Transferase.
FT CHAIN 1..405
FT /note="Prenyltransferase phqA"
FT /id="PRO_0000448863"
FT BINDING 195
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 262
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 332
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
SQ SEQUENCE 405 AA; 45359 MW; DE77A211988D34F5 CRC64;
MGSINIVTPY MKIGQYLSFR NRDHFSWWHQ KGPVLSQMLQ ACHYGVHEQY QYLTLFYAHL
IPALGAYTEP SVGQKGNTLL SGAGRLELSR TFTVDDSSLR IAFEPTSFLA SEKGTDPLNR
VPLSRLLSVL GQLSGVSLGT DRYRTLADQL TTSDDDEEKL LNEPTLAEQL QSLPSRTQNI
LALELVNGFV KPELYFHPQM KALASGALVE DLLFDALRSV DSAGRLGKAI DLAKEFVQAA
PTTTRPQFIS YQIERSHSGA AKLFLTESAI NWDQISGLWR YAQPETIQTE QNRALRVLWE
SLNVVEGNRG PNQFPIMMVL GLFAEEPFVR PQVAFPVVGM TEGAIARSIG RFFDNMGWKE
SSQSYVDGLR SYFPNEDLDQ PLGKQAWVAL SLFDSENPAL TVFYY
