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Mycolic Acid Cyclopropane Synthase Enzymes as New Biocatalysts for Green Cyclopropanation Reactions

Project description

Sustainable cyclopropane synthases using mycobacterial enzymes

Many chemicals, fragrances, pharmaceuticals, and natural products require cyclopropane rings, a crucial structural motif in their synthesis. Unfortunately, current manufacturing methods for cyclopropane-containing molecules are often unsafe and unsustainable. Existing alternative approaches are limited because they rely on repurposed or artificial haem enzymes, which require stoichiometric amounts of hazardous diazo-compound reagents as co-substrates. With the support of the Marie Skłodowska-Curie Actions programme, the MyCyclop project will characterise and develop mycolic-acid cyclopropane synthases. This is a cyclopropane synthase enzyme found in mycobacteria and could offer a sustainable and efficient alternative to current cyclopropane-containing molecule manufacture. These insights are expected to open up new possibilities for biocatalyst development.

Objective

"Cyclopropane rings are a key structural motif that may be found in a wide range of natural products, chemicals, fragrances and pharmaceuticals. Current methods for the manufacturing of cyclopropane-containing molecules show significant limitations in terms of safety, environmental impact and green metrics. Only a few biocatalytic methodologies for the asymmetric synthesis of cyclopropanes have been developed so far, and they rely on repurposed or artificial heme enzymes (P450, myoglobin). However, these approaches suffer from significant limitations in terms of ""green chemistry"" and industrial application since they require stoichiometric amounts of hazardous diazo-compound reagents as co-substrates. Overcoming these limitations is a critical challenge that underscores the need for further research and development in 'green chemistry' and industrial application of biocatalysis. Mycolic Acid Cyclopropane Synthases (MACSs) are pivotal cyclopropane synthase enzymes found in mycobacteria, such as M. tuberculosis. They are a group of homologous enzymes in the mycolic acid biosynthesis pathway, and they are crucial in catalysing the cyclopropanation of double bonds. Since MACSs use S-adenosyl-L-methionine (SAM) as a methylene donor rather than diazo-carbene co-substrates, they present a viable option for creating mild and sustainable cyclopropanation biocatalysts. Furthermore, with their ability to catalytic cyclopropanate short- to long-chain unsaturated fatty acids and their ease of bioengineering, these enzymes present a novel and exciting opportunity for future biocatalyst development. This project focuses on the characterization and development of MACSs as cyclopropanating biocatalysts through enzyme engineering approaches."

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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-2024-PF-01

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Coordinator

UNIVERSITY COLLEGE LONDON
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.

€ 276 187,92
Address
GOWER STREET
WC1E 6BT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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