De novo biosynthesis of sakuranetin from glucose by engineered Saccharomyces cerevisiae.
Appl Microbiol Biotechnol
; 107(12): 3899-3909, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-37148336
ABSTRACT
Sakuranetin is a plant-natural product, which has increasingly been utilized in cosmetic and pharmaceutical industries for its extensive anti-inflammatory, anti-tumor, and immunomodulatory effects. Sakuranetin was mostly produced by extraction technology from plants, which is limited to natural conditions and biomass supply. In this study, a de novo biosynthesis pathway of sakuranetin by engineered S. cerevisiae was constructed. After a series of heterogenous gene integration, a biosynthetic pathway of sakuranetin from glucose was successfully constructed in S. cerevisiae whose sakuranetin yield reached only 4.28 mg/L. Then, a multi-module metabolic engineering strategy was applied for improving sakuranetin yield in S. cerevisiae (1) adjusting the copy number of sakuranetin synthesis genes, (2) removing the rate-limiting factor of aromatic amino acid pathway and optimizing the synthetic pathway of aromatic amino acids to enhance the supply of carbon flux for sakuranetin, and (3) introducing acetyl-CoA carboxylase mutants ACC1S659A,S1157A and knocking out YPL062W to strengthen the supply of malonyl-CoA which is another synthetic precursor of sakuranetin. The resultant mutant S. cerevisiae exhibited a more than tenfold increase of sakuranetin titer (50.62 mg/L) in shaking flasks. Furthermore, the sakuranetin titer increased to 158.65 mg/L in a 1-L bioreactor. To our knowledge, it is the first report on the sakuranetin de novo synthesis from glucose in S. cerevisiae. KEY POINTS ⢠De novo biosynthesis of sakuranetin was constructed by engineered S. cerevisiae. ⢠Sakuranetin production was enhanced by multi-module metabolic engineering strategy. ⢠It is the first report on the sakuranetin de novo synthesis in S. cerevisiae.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
/
Glucose
Idioma:
En
Revista:
Appl Microbiol Biotechnol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China