Genetic engineering and molecular characterization of yeast strain expressing hybrid human-yeast squalene synthase as a tool for anti-cholesterol drug assessment.
PBN-AR
Instytucja
Instytut Biochemii i Biofizyki Polskiej Akademii Nauk
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
EN
Czasopismo
Journal of applied microbiology
ISSN
1364-5072
EISSN
1365-2672
Wydawca
Wiley-Blackwell
DOI
Rok publikacji
2016
Numer zeszytu
4
Strony od-do
877-888
Numer tomu
120
Link do pełnego tekstu
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
EN
heterologous proteins;
mevalonate pathway;
squalene synthase;
sterol biosynthesis inhibitors;
yeast expression system
Streszczenia
Język
EN
Treść
AIMS The main objective of the study is molecular and biological characterization of the human-yeast hybrid squalene synthase (SQS), as a promising target for treatment of hypercholesterolaemia. METHODS AND RESULTS The human-yeast hybrid SQS, with 67% amino acids, including the catalytic site derived from human enzyme, was expressed in Saccharomyces cerevisiae strain deleted of its own SQS gene. The constructed strain has a decreased level of sterols compared to the control strain. The mevalonate pathway and sterol biosynthesis genes are induced and the level of triacylglycerols is increased. Treatment of the strain with rosuvastatin or zaragozic acid, two mevalonate pathway inhibitors, decreased the amounts of squalene, lanosterol and ergosterol, and up-regulated expression of several genes encoding enzymes responsible for biosynthesis of ergosterol precursors. Conversely, expression of the majority genes implicated in the biosynthesis of other mevalonate pathway end products, ubiquinone and dolichol, was down-regulated. CONCLUSIONS The S. cerevisiae strain constructed in this study enables to investigate the physiological and molecular effects of inhibitors on cell functioning. SIGNIFICANCE AND IMPACT OF THE STUDY The yeast strain expressing hybrid SQS with the catalytic core of human enzyme is a convenient tool for efficient screening for novel inhibitors of cholesterol-lowering properties.
Inne
System-identifier
5224
CrossrefMetadata from Crossref logo
Cytowania
Liczba prac cytujących tę pracę
Brak danych
Referencje
Liczba prac cytowanych przez tę pracę
Brak danych