Enhancing the yield of industrial Actinomycete fermentations

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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.