The University of Amsterdam (UvA) and the University of Perugia (UniPG) have recently signed a 4-year agreement for a joined PhD project in the area of sustainable synthesis of steroids using novel chemo-enzymatic strategies and flow technology. The cooperation harnesses the expertise of the laboratory of Medicinal and Advanced Synthetic Chemistry led by professor Antimo Gioiello at UniPG Department of Pharmaceutical Sciences, and the Biocatalysis lab led by professor Francesco Mutti at the UvA's Van 't Hoff Institute for Molecular Sciences.
Gioiello's MASC lab contributes with expertise in the field of steroids synthesis and continuous flow chemistry, whereas Mutti's HIMS-Biocat group contributes with expertise in the area of organic synthesis using enzymes and enzyme engineering. This creates the ideal synergy for the success of the project and the training of the PhD candidate in the area of flow biocatalysis.
Hard to synthesise
Steroids are ubiquitous in nature and perform essential vital functions. An example is the regulation of hormonal activity or the digestion and absorption of lipids. Steroids are fundamental constituents of cell membranes and can exhibit anti-inflammatory, antitumor, antiviral, antimicrobial and antifungal activities. They can also be used to treat other clinical conditions including cardiovascular diseases and obesity. The global market for steroidal drugs and intermediates is estimated at more than $ 10 billion.
However, many steroid molecules are difficult to synthesise via traditional organic chemistry which requires many synthetic steps and displays low yields. To render these molecules more accessible for clinical trials and mass drug production, new atom-efficient and chemoselective synthesis methods are urgently needed. Such new processes for steroids manufacture must also meet modern synthesis standards such as sustainability, safety and cost.
Flow biocatalytic systems
The joined PhD project aims to address this challenge by developing integrated flow chemo-biocatalytic systems for the remote functionalisation of steroids. The main goals are:
- to develop and apply new enzymes for the site-specific functionalisation of steroids (e.g., sulphation, C-H hydroxylation, amination);
- to implement the new biocatalysts into tailored chemical routes to shorten the number of synthesis steps, enhance efficiency and reduce waste;
- to develop innovative flow-bioreactors that enable robust and scalable processes for the synthesis of steroids.
In this context, the recruited PhD student Elena Tomarelli will have the opportunity to learn advanced organic synthesis including steroid chemistry, biocatalysed reactions, enzyme engineering, recombinant enzyme production, design and realisation of continuous flow processes, method optimisation and automation. Tomarelli will work alternating periods in the Amsterdam and Perugia laboratories.
