YcascadE | Design and creation of a yeast platform for synthesis of chiral amines by enzymatic cascades

Summary
The development of green and robust technologies for the conversion of renewable feedstock into high-value chemicals is of great interest and challenging for the chemical industry. Although L-α-amino acids can be sustainably produced from renewable feedstock by fermentation, these amino acids are rarely being used as starting material for the chemical synthesis of high-value chiral molecules due to the lack of efficient and highly selective biocatalytic methodologies . In this project, I will design and develop a modular approach for biocatalysis in vivo enabling the conversion of natural amino acids into enantiopure alpha-chiral amines and amino-alcohols, which are important intermediates or final products for the pharmaceutical, agrochemical and fine chemical industries. Saccharomyces cerevisiae will be selected as the host organism for the biocatalytic pathway because its genome is well-known, is suitable for large scale operation, and will allow to obtain higher productivity than using bacterial strains. A library of integrative plasmids expressing the enzymes will be constructed and transformed to S. cerevisiae to obtain a yeast cell factory. The system will be optimized both on the genetic level and on the bioprocess level. The working plan will include an interdisciplinary approach involving molecular biology techniques together with metabolic engineering as well as optimization of conditions for biotransformation. Additionally, analytical chemistry methodologies for determination of yield, purity and enantiomeric excess of the products and intermediates will be required. While the state-of-the-art proves the feasibility of the project, by using our proposed approach with resting S. cerevisiae cells, we expect to make a major break-through in the field in terms of increase productivity (e.g., space-yield; space-time-yield; total yields from substrate) and, moreover, a wider applicability of the resulting platform due to the modularity approach.
Unfold all
/
Fold all
More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101153173
Start date: 01-03-2025
End date: 28-02-2027
Total budget - Public funding: - 203 464,00 Euro
Cordis data

Original description

The development of green and robust technologies for the conversion of renewable feedstock into high-value chemicals is of great interest and challenging for the chemical industry. Although L-α-amino acids can be sustainably produced from renewable feedstock by fermentation, these amino acids are rarely being used as starting material for the chemical synthesis of high-value chiral molecules due to the lack of efficient and highly selective biocatalytic methodologies . In this project, I will design and develop a modular approach for biocatalysis in vivo enabling the conversion of natural amino acids into enantiopure alpha-chiral amines and amino-alcohols, which are important intermediates or final products for the pharmaceutical, agrochemical and fine chemical industries. Saccharomyces cerevisiae will be selected as the host organism for the biocatalytic pathway because its genome is well-known, is suitable for large scale operation, and will allow to obtain higher productivity than using bacterial strains. A library of integrative plasmids expressing the enzymes will be constructed and transformed to S. cerevisiae to obtain a yeast cell factory. The system will be optimized both on the genetic level and on the bioprocess level. The working plan will include an interdisciplinary approach involving molecular biology techniques together with metabolic engineering as well as optimization of conditions for biotransformation. Additionally, analytical chemistry methodologies for determination of yield, purity and enantiomeric excess of the products and intermediates will be required. While the state-of-the-art proves the feasibility of the project, by using our proposed approach with resting S. cerevisiae cells, we expect to make a major break-through in the field in terms of increase productivity (e.g., space-yield; space-time-yield; total yields from substrate) and, moreover, a wider applicability of the resulting platform due to the modularity approach.

Status

SIGNED

Call topic

HORIZON-MSCA-2023-PF-01-01

Update Date

22-11-2024
Images
No images available.
Geographical location(s)
Structured mapping
Unfold all
/
Fold all
Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2023-PF-01
HORIZON-MSCA-2023-PF-01-01 MSCA Postdoctoral Fellowships 2023