Luca Ferrarotto

The increasing threat of antibiotic resistance highlights the urgent need for the discovery and development of new antimicrobial therapies, many of which originate from microbial biosynthetic pathways. Streptomyces, a genus of filamentous Gram-positive bacteria, is the source of over 60% of clinically used antimicrobials. In addition, it represents a promising platform for heterologous protein expression, particularly for proteins involved in antimicrobial biosynthesis.

Streptomyces retains several key metabolic and genomic features that make it an ideal host for producing complex and recalcitrant proteins involved in the biosynthesis of natural products. These features include the ability to perform complex post-translational modifications (PTMs) and to support the expression of genes with high G+C content.

The main focus of Luca’s project is the development of a bifunctional expression vector engineered for plasmid manipulation in Escherichia coli and efficient protein production in Streptomyces, without compromising plasmid stability or protein yield. The project also applies biochemical, biophysical, and structural approaches to characterize enzymes produced using this system that have proven recalcitrant in other well-established expression systems.

This work lays the groundwork for a standardised protein expression platform in Streptomyces while helping to overcome current limitations in the production and characterisation of proteins relevant to the discovery and development of new antimicrobial agents.