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New Carbohydrate Oxidising Enzymes prepared by directed evolution and their application in synthesis of AminoGlycoside derivatives with antibiotic potential and rare sugars.

Project description

Engineered enzymes for the synthesis of compounds to combat antimicrobial resistance

Carbohydrate-oxidising enzymes (COEs) are specialised proteins that modify carbohydrates by oxidising specific hydroxyl positions on their sugar rings, using oxygen as a mild oxidant. Their ability to target specific sites depends on the active site’s structure. This renders them highly selective tools for sugar modification. With the support of the Marie Skłodowska-Curie Actions programme, the COxEnzymes - AGs project will engineer COEs to be applied in the regioselective synthesis of a library of bioactive compounds. Such compounds include aminoglycoside derivatives to combat antimicrobial resistance and rare sugars that can benefit health. The proposed approach will enable rapid and efficient creation of a large library of compounds that will be tested for antimicrobial activity and evaluated statistically. Project activities will have implications for biotechnology and chemistry.

Objective

Carbohydrate-oxidising enzymes (COE) are a group of enzymes which are active on specific carbohydrates and can use molecular oxygen as a mild oxidant. Oxidation is typically directed towards specific positions of the sugar ring. Regioselectivity and substrate specificity relies on the architecture of active site, therefore the direct evolution approach in this project will allow to generate a toolbox of effective and regiospecific catalysts to modify various carbohydrate scaffolds. Our aim is to use this toolbox to generate a library of bioactive compounds: i) aminoglycoside derivatives starting with analogues of Kanamycin as candidates to help in the fight against the global problem of antimicrobial resistance. This process in combination with a further chemical step may lead to a large library of derivatives prepared in short time with only a two-step chemoenzymatic process; ii) rare monosaccharides and oligosaccharides as promising candidates with health benefits. Antimicrobial activities of prepared library of compounds will be measured and statistically evaluated. Furthermore, this project will advance the current knowledge of COE which is of utmost interest for fundamental biology and crucial for industrial biotechnology and chemistry applications. Biocatalysis will be applicable to the synthesis of a wide range of saccharide related compounds, solving one of the big challenges in carbohydrate chemistry, the regioselective differentiation of the OH groups, in a green, sustainable and very efficient way.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

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

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Coordinator

UNIVERSIDADE NOVA DE LISBOA
Net EU contribution
€ 172 618,56
Address
CAMPUS DE CAMPOLIDE
1099-085 Lisboa
Portugal
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data