Metabolic engineering of Saccharomyces cerevisiae for enhanced taxadiene production
Journal article, 2024

Background: Metabolic engineering enables the sustainable and cost-efficient production of complex chemicals. Efficient production of terpenes in Saccharomyces cerevisiae can be achieved by recruiting an intermediate of the mevalonate pathway. The present study aimed to evaluate the engineering strategies of S. cerevisiae for the production of taxadiene, a precursor of taxol, an antineoplastic drug. Result: SCIGS22a, a previously engineered strain with modifications in the mevalonate pathway (MVA), was used as a background strain. This strain was engineered to enable a high flux towards farnesyl diphosphate (FPP) and the availability of NADPH. The strain MVA was generated from SCIGS22a by overexpressing all mevalonate pathway genes. Combining the background strains with 16 different episomal plasmids, which included the combination of 4 genes: tHMGR (3-hydroxy-3-methylglutaryl-CoA reductase), ERG20 (farnesyl pyrophosphate synthase), GGPPS (geranyl diphosphate synthase) and TS (taxadiene synthase) resulted in the highest taxadiene production in S. cerevisiae of 528 mg/L. Conclusion: Our study highlights the critical role of pathway balance in metabolic engineering, mainly when dealing with toxic molecules like taxadiene. We achieved significant improvements in taxadiene production by employing a combinatorial approach and focusing on balancing the downstream and upstream pathways. These findings emphasize the importance of minor gene expression modification levels to achieve a well-balanced pathway, ultimately leading to enhanced taxadiene accumulation.

Terpenes

Mevalonate pathway

Metabolic engineering

S. cerevisiae

Taxol

Author

Hülya Karaca Gencer

Anadolu Üniversitesi

Chalmers, Life Sciences, Systems and Synthetic Biology

Murat Kaya

Anadolu Üniversitesi

Handan Açelya Kapkac

Eskisehir Technical University

Serkan Levent

Anadolu Üniversitesi

Yusuf Ozkay

Anadolu Üniversitesi

Secil Deniz Ozan

Anadolu Üniversitesi

Jens B Nielsen

Chalmers, Life Sciences, Systems and Synthetic Biology

Anastasia Krivoruchko

Chalmers, Life Sciences, Systems and Synthetic Biology

Microbial Cell Factories

14752859 (eISSN)

Vol. 23 1 241

Subject Categories

Microbiology

DOI

10.1186/s12934-024-02512-z

More information

Latest update

9/25/2024