Cyclopropane rings—three-carbon triangles found in many pharmaceuticals, flavours, and fragrances—are currently built using harsh chemicals, toxic reagents, and energy-intensive conditions. This project aims to replace those methods with enzymes called 2-ODDs, which can form cyclopropane rings under mild, water-based conditions using only iron sulfate and a cheap co-substrate. The problem is that existing synthetic routes rely on hazardous diazo compounds, stoichiometric metals like zinc or butyllithium, and chiral auxiliaries—none of which are sustainable or suitable for industrial scale-up. The gap is that no one has yet turned these particular 2-ODD enzymes into practical biocatalysts for cyclopropanation. If successful, the research would give chemists a greener, cheaper way to make cyclopropane-containing drug ingredients and flavour compounds. That could reduce toxic waste and energy use in pharmaceutical and fine-chemical manufacturing—industries that quietly underpin medicines, cosmetics, and food production. This is fundamental enzymology and biocatalyst engineering. The two enzymes, BeIL and HrmJ, will be characterised, then improved through genome mining, computational modelling, and directed evolution. Similar fundamental work on other enzymes has already replaced toxic metal catalysts in several industrial processes.
View original technical description
The cyclopropane ring is a highly versatile synthetic intermediate and a valuable structural motif present in many pharmaceutical ingredients and bioactive natural products, as well as in flavours and fragrances. Given its wide use and significance in organic chemistry, several synthetic approaches, including biocatalytic methods, have been developed to synthesize cyclopropane-containing compounds. However, the currently available synthetic methodologies suffer from major limitations in terms of "green chemistry" and industrial application since they require harsh reaction conditions, stoichiometric metal mediators (Zn, BuLi), chiral auxiliaries, and hazardous diazo-compound reagents. This project aims to characterize and exploit 2-oxoglutarate/Fe(II)-dependent dioxygenase (2-ODD) enzymes as biocatalysts for milder and more sustainable cyclopropanation biotransformations. The 2-ODD enzymes catalyze a wide range of chemical transformations, including complex skeletal rearrangements, ring expansions, and C-C bond formation through C-H activation, including cyclopropane formation. One of the advantages of 2-ODD enzymes is the fact that they operate under mild conditions, and they need only 2-oxoglutarate as a co-substrate and the green and cheap cofactor FeSO4. These features and their catalytic versatility make 2-ODDs attractive enzymes for future biocatalyst development. Within this project, two 2-ODD enzymes, BeIL and HrmJ, endowed with cyclopropanation activity, will be investigated and fully characterized, and through genome and metagenome mining, computational and mutagenesis studies, they will be turned into sustainable biocatalysts for cyclopropanation reactions. This highly interdisciplinary project lies on the edge of organic chemistry, enzymology and chemical engineering and will contribute to enlarge the toolbox of synthetically useful biocatalysts for chemical processes, which represents a key European research priority.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know