Integrated biocatalytic approaches enabling steroids synthesis and functionalization

Steroids are ubiquitous in nature and perform essential vital functions such as the regulation hormonal activity or the digestion and absorption of lipids. Steroids are also fundamental constituents of cell membranes and can exhibit anti-inflammatory, antitumor, antiviral, antimicrobial, and antifungal activities with important therapeutic applications in the treatment of several clinical conditions including cardiovascular diseases and obesity. Not surprisingly, the global market for steroidal drugs and intermediates has a remarkable value of more than 10 billion US dollars. Despite their impressive distribution, the production of many steroid molecules remains difficult via traditional organic chemistry, displaying many synthetic steps, low yields and selectivity. Given the urge to make these molecules more accessible for clinical trials and drug manufacturing, new atom-efficient and chemo-selective synthesis methods are highly desired. Such new processes must also meet modern synthesis standards such as sustainability, safety, and cost efficiency. For this purpose, in this joined PhD project we aimed to address this challenge by developing integrated flow chemo-biocatalytic systems for steroid functionalization. In particular, the major aims of the project are:
• Discover and apply new enzymes for the site-specific functionalization of steroids under mild conditions (e.g., sulphation, amination)
• Implement new biocatalysts into tailored chemical routes to shorten the number of synthesis steps, enhance efficiency, and reduce waste.
This project benefited by the collaboration between the Laboratory of Medicinal and Advanced Synthetic Chemistry led by Professor Antimo Gioiello at UniPG Department of Pharmaceutical Sciences with sustainable and flow synthesis of steroids and the Biocatalysis lab led by Professor Francesco Mutti at the UvA's Van 't Hoff Institute for Molecular Sciences, with organic synthesis using enzymes and enzyme engineering.