Understanding the development of Industrial strain lineages

了解工业菌株谱系的发展

• 批准号: 2307815
• 金额: --
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2307815
• 关键词: Understanding; development; 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.

摘要：克拉维酸(CA)是一种β-内酰胺酶抑制剂，能够增强青霉素类药物对其他耐药细菌的抗菌活性。它是在棒状链霉菌中自然发现的复杂生物工厂的产物，目前是通过发酵生产的，使用的是一种经过连续几轮菌株改良的菌株。发酵条件和培养基经过精心控制和优化，以确保最大限度地促进细胞生长和CA产量，但生物工厂及其基因组是CA生产商业化成功的关键。拟议的工作旨在使用基因组测序来实现与高价值GSK棒状链霉菌菌株谱系中的菌株进行比较基因组学，从而能够确定关键的基因组过渡。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，并将揭示关键的基因组特征，这些特征可能会转移到其他抗生素生产生物体。