Understanding the development of Industrial strain lineages

Summary: Clavulanic acid (CA) is a beta-lactamase inhibitor able to potentiate the antibacterial activity of penicillins against otherwise resistant bacteria. It is the product of complex biological factories found naturally in Streptomyces clavuligerus, and is currently made industrially via fermentation using a strain that has been through successive rounds of strain improvement. Fermentation conditions and media are carefully controlled and optimised to ensure maximum cell growth and CA production, yet the biological factory and its genome is key to commercially successful CA production. The proposed work aims to use genome sequencing to enable comparative genomics to be performed with strains in the high-value GSK Streptomyces clavuligerus strain lineage to enable key genomic transitions to be identified. This project will elucidate key genetic changes that lead to improved CA production in Streptomyces fermentation and will reveal key genomic features that may be transferable to other antibiotic producing organisms.