CycloproBio · Cyclopropane Synthase Enzymes as Biocatalysts for Green Cyclopropanation Reactions
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2022-01-01 → 2024-01-16
- Финансиране от ЕС
- 224 934 €
- Участници
- 2
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Ензимите циклопропан синтаза се изследват като биологични катализатори за синтез на мастни киселини и фосфолипиди. Това помага за намаляване на вредните вещества и тежките условия при производството на лекарства и химикали.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Cyclopropane Synthase Enzymes as Biocatalysts for Green Cyclopropanation Reactions
Cyclopropane rings are a structural element naturally occurring in biologically active natural products compounds and pharmaceutical ingredients.The rigidity of its constrained structure and its reactivity make it a unique structural motif of interest in pharmaceutical science, synthetic chemistry, chemical biology. Due to their wide interest, several different synthetic methodologies have been developed over time, to prepare cyclopropanes, as racemates or in enantiomerically pure form, including, among the most important, the Simmons-Smith and the Corey–Chaykovsky reactions. More recently, enzymatic cyclopropanation methodologies ,using engineered variants of the cytochrome P450-BM3, myoglobin-based catalyst, for highly selective cyclopropanation reactions of different compounds. However, all this methodologies still suffers major synthetic and environmental limitations due to the use of harsh reaction conditions, stoichiometric metal mediators or chiral auxiliaries and hazardous diazo-compound reagents. Ultimately, cyclopropanation is still a major challenge in organic chemistry. To tackle this issue in terms of "green chemistry" and industrial application, Cyclopropane Synthase (CS) enzymes constitute an interesting class of enzymes, naturally catalysing the cyclopropanation of unsaturated lipids in bacteria and plants , operating under milder conditions and without using hazardous diazo-carbene co-substrates. Cycloprobio has characterised new CS enzymes and paved the way to their exploitation as biocatalysts for selective synthesis of cyclopropanated fatty acids and phospholipids. This ultimately is expected to contribute in reducing the environmental impact of a variety of chemical and pharmaceutical manufacturing processes. The project also firmly aligns with the key European research priorities of “green chemistry” and “sustainable manufacturing processes”.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The cyclopropane ring is an important structural motif present in many pharmaceutical compounds and widely used as reactive building blocks in the synthesis of chemicals. Many synthetic strategies to access cyclopropanes have been developed to date, most of which typically require the use of potentially explosive diazo-carbene compounds as substrates. Even recently proposed enzymatic transformations, exploiting cytochromes P450 and myoglobin, require the use of stoichiometric carbene co-substrates, thus narrowing their industrial applications. The CycloproBio project aims to explore cyclopropane synthase (CS) enzymes as a potentially mild method for biocatalytic cyclopropanation. Cyclopropane synthases are SAM dependent transferase enzymes able to catalyse cyclopropanation of unsaturated phospholipids in bacterial membranes. Even if CS are common to most bacteria, many questions on factors affecting their substrate selectivity remain unanswered. Moreover, despite their potential, CS enzymes have not been explored yet as potential biocatalysts. This project will initially characterize the cyclopropane fatty acid synthase (CFAS) from E. coli which has been cloned, expressed and purified in preliminary work. The catalytic properties of the E. coli CFAS will be studied through the development of an appropriate activity assay, the investigation of its substrate specificity and the study of its physio-chemical properties. To broaden the study, genome mining for other CS enzymes from different bacterial species will be carried out to gain insight into the factors which affect the selectivity of these enzymes. Finally, new CS enzyme variants will be generated through rational mutagenesis of putative substrate binding residues. The data generated will provide fundamental information on the CS family. The primary aim of this project is to use this data to develop cyclopropanation biocatalysts for the sustainable synthesis of chemicals and pharmaceuticals.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY COLLEGE LONDON · LondonКоординаторОбединеното кралство
- KING'S COLLEGE LONDON · LondonОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз