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Controlling growth and morphogenesis of the industrial enzyme producer Streptomyces lividans

Promotor: G.P. van Wezel, Co-Promotor: E. Vijgenboom

G. Mangiameli
12 juni 2014
Thesis in Leiden Repository

Streptomyces are Gram-positive, soil dwelling bacteria that raised interest in the last 50 years for their high potential in antibiotic and protein production. Thanks to their saprophytic nature, streptomycetes secrete a massive amount of industrial enzymes. They have a relatively low level of endogenous extracellular proteolytic activity when compared to other expression hosts (e.g. Bacillus), they are generally more suited to produce proteins encoded by high G+C actinomycete genes in their native form, coupled to efficient secretion so as to avoid that the proteins end up in inclusion bodies (often a problem when using e.g. E. coli) and making downstream processes easier. Despite their attractive potential, Streptomyces present several constraints which so far limit their application in industry. The first constraint is morphology: by growing as a network of hyphae, they produce dense pellets in liquid cultures that hold Streptomyces back from being one of the first choice cell factories in large scale fermentations. In addition, the limited availability of efficient expression systems for high-level transcription/translation and subsequent secretion is a further bottleneck. This thesis presents the work done to address these issues for the optimization of Streptomyces lividans for future industrial applications and enzyme production.