Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 9428-9437 |
| Journal | Journal of the American Chemical Society |
| Volume | 134 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 2012 |
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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 journal › Article
TY - JOUR
T1 - Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferases
AU - Chooi, Heng
AU - Wang, P.
AU - Fang, J.
AU - Li, Y.
AU - Wu, K.
AU - Tang, Y.
PY - 2012
Y1 - 2012
N2 - 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.
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.
U2 - 10.1021/ja3028636
DO - 10.1021/ja3028636
M3 - Article
VL - 134
SP - 9428
EP - 9437
JO - Journal of the Amercian Chemical Society
JF - Journal of the Amercian Chemical Society
SN - 0002-7863
IS - 22
ER -