Understanding the development of Industrial strain lineages

摘要：克拉维酸（CA）是一种β -内酰胺酶抑制剂，能够增强青霉素对其他耐药细菌的抗菌活性。它是在棒状链霉菌中天然发现的复杂生物工厂的产物，目前是通过使用经过连续几轮菌株改进的菌株发酵而工业生产的。发酵条件和培养基经过精心控制和优化，以确保最大限度的细胞生长和CA产量，但生物工厂及其基因组是商业上成功生产CA的关键。提出的工作旨在使用基因组测序，使比较基因组学能够在高价值GSK链霉菌棒状菌菌株谱系中进行，以使关键的基因组转换能够被识别。该项目将阐明导致链霉菌发酵中CA产量提高的关键遗传变化，并将揭示可能转移到其他抗生素生产生物的关键基因组特征。

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.