Enhancing the yield of industrial Actinomycete fermentations

英国需要一种新的、激进的菌株构建方法，以保持在生产非专利抗生素方面的竞争力。抗生素发酵过程平衡营养和细胞生长速率与化学和物理环境。传统上通过选择高产突变体和优化发酵培养基来提高细胞产量。然而，许多抗生素在细胞外环境中是不稳定的，pH和降解速率之间具有良好的特征关系。生物系统运行的pH值范围通常与产品的最佳化学稳定性相冲突。对于已建立的商业工艺，我们建议利用合成生物学和基因组学的最新进展来开发能够在较低pH下操作的细菌菌株和工业发酵工艺，从而促进所需产品的稳定性。

A new and radical approach to strain construction is needed for the UK to remain competitive in manufacturing off-patent antibiotics. Antibiotic fermentation processes balance nutrients and cell growth rate with the chemical and physical environments. Cellular output is traditionally improved by selecting higher-producing mutants and optimising fermentation media. However, many antibiotics are unstable in the extracellular environment, with well characterised relationships between pH and degradation rate. The pH range for operation of the biological system often conflicts with the optimum for chemical stability of the product. For an established commercial process we propose to utilise recent advances in synthetic biology and genomics to develop a bacterial strain and industrial fermentation process capable of operating at a lower pH, facilitating stability of the desired product.