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

Project description

Yeast biocatalysis for chemical synthesis

Valuable chemicals serve as building blocks in the pharmaceutical and agrochemical industry for the manufacturing of various products. L amino acids play a significant role in high-value chiral molecule synthesis due to their versatile chemical structure. However, technical challenges limit the utilisation of L amino acids in chemical synthesis, necessitating alternative technologies. Funded by the Marie Skłodowska-Curie Actions programme, the YcascadE project proposes to develop a modular biocatalysis approach in vivo using the yeast Saccharomyces cerevisiae. The idea is to harness the specificity of enzymes in a sustainable and high-yield approach to produce intermediates for the chemical industry.

Objective

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

UNIVERSITEIT VAN AMSTERDAM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 203 464,32
Total cost

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