Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferases

Heng Chooi, P. Wang, J. Fang, Y. Li, K. Wu, Y. Tang

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The prenyltransferase (PTase) gene vrtC was proposed to be involved in viridicatumtoxin (1) biosynthesis in Penicillium aethiopicum. Targeted gene deletion and reconstitution of recombinant VrtC activity in vitro established that VrtC is a geranyl transferase that catalyzes a regiospecific Friedel-Crafts alkylation of the naphthacenedione carboxamide intermediate 2 at carbon 6 with geranyl diphosphate. VrtC can function in the absence of divalent ions and can utilize similar naphthacenedione substrates, such as the acetyl-primed TAN-1612 (4). Genome mining using the VrtC protein sequence leads to the identification of a homologous group of PTase genes in the genomes of human and animal-associated fungi. Three enzymes encoded by this new subgroup of PTase genes from Neosartorya fischeri, Microsporum canis, and Trichophyton tonsurans were shown to be able to catalyze transfer of dimethylallyl to several tetracyclic naphthacenedione substrates in vitro. In total, seven C 5- or C 10-prenylated naphthacenedione compounds were generated. The regioselectivity of these new polycyclic PTases (pcPTases) was confirmed by characterization of product 9 obtained from biotransformation of 4 in Escherichia coli expressing the N. fischeri pcPTase gene. The discovery of this new subgroup of PTases extends our enzymatic tools for modifying polycyclic compounds and enables genome mining of new prenylated polyketides. © 2012 American Chemical Society.
Original languageEnglish
Pages (from-to)9428-9437
JournalJournal of the American Chemical Society
Volume134
Issue number22
DOIs
Publication statusPublished - 2012

Fingerprint

Dimethylallyltranstransferase
Polyketides
Genes
Neosartorya
Triacetoneamine-N-Oxyl
Genome
Polycyclic Compounds
Microsporum
Trichophyton
Penicillium
Gene Deletion
Alkylation
Human Genome
Biotransformation
Transferases
Fungi
Carbon
Ions
Escherichia coli
Regioselectivity

Cite this

Chooi, Heng ; Wang, P. ; Fang, J. ; Li, Y. ; Wu, K. ; Tang, Y. / Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferases. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 22. pp. 9428-9437.
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abstract = "The prenyltransferase (PTase) gene vrtC was proposed to be involved in viridicatumtoxin (1) biosynthesis in Penicillium aethiopicum. Targeted gene deletion and reconstitution of recombinant VrtC activity in vitro established that VrtC is a geranyl transferase that catalyzes a regiospecific Friedel-Crafts alkylation of the naphthacenedione carboxamide intermediate 2 at carbon 6 with geranyl diphosphate. VrtC can function in the absence of divalent ions and can utilize similar naphthacenedione substrates, such as the acetyl-primed TAN-1612 (4). Genome mining using the VrtC protein sequence leads to the identification of a homologous group of PTase genes in the genomes of human and animal-associated fungi. Three enzymes encoded by this new subgroup of PTase genes from Neosartorya fischeri, Microsporum canis, and Trichophyton tonsurans were shown to be able to catalyze transfer of dimethylallyl to several tetracyclic naphthacenedione substrates in vitro. In total, seven C 5- or C 10-prenylated naphthacenedione compounds were generated. The regioselectivity of these new polycyclic PTases (pcPTases) was confirmed by characterization of product 9 obtained from biotransformation of 4 in Escherichia coli expressing the N. fischeri pcPTase gene. The discovery of this new subgroup of PTases extends our enzymatic tools for modifying polycyclic compounds and enables genome mining of new prenylated polyketides. {\circledC} 2012 American Chemical Society.",
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Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferases. / Chooi, Heng; Wang, P.; Fang, J.; Li, Y.; Wu, K.; Tang, Y.

In: Journal of the American Chemical Society, Vol. 134, No. 22, 2012, p. 9428-9437.

Research output: Contribution to journalArticle

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AU - Chooi, Heng

AU - Wang, P.

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AU - Li, Y.

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AU - Tang, Y.

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AB - The prenyltransferase (PTase) gene vrtC was proposed to be involved in viridicatumtoxin (1) biosynthesis in Penicillium aethiopicum. Targeted gene deletion and reconstitution of recombinant VrtC activity in vitro established that VrtC is a geranyl transferase that catalyzes a regiospecific Friedel-Crafts alkylation of the naphthacenedione carboxamide intermediate 2 at carbon 6 with geranyl diphosphate. VrtC can function in the absence of divalent ions and can utilize similar naphthacenedione substrates, such as the acetyl-primed TAN-1612 (4). Genome mining using the VrtC protein sequence leads to the identification of a homologous group of PTase genes in the genomes of human and animal-associated fungi. Three enzymes encoded by this new subgroup of PTase genes from Neosartorya fischeri, Microsporum canis, and Trichophyton tonsurans were shown to be able to catalyze transfer of dimethylallyl to several tetracyclic naphthacenedione substrates in vitro. In total, seven C 5- or C 10-prenylated naphthacenedione compounds were generated. The regioselectivity of these new polycyclic PTases (pcPTases) was confirmed by characterization of product 9 obtained from biotransformation of 4 in Escherichia coli expressing the N. fischeri pcPTase gene. The discovery of this new subgroup of PTases extends our enzymatic tools for modifying polycyclic compounds and enables genome mining of new prenylated polyketides. © 2012 American Chemical Society.

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