Abstract
Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients’ depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.
Highlights
The overproduction of homologous and heterologous proteins for pharmacological and industrial application requires the use of different prokaryotic and eukaryotic expression systems
Gram-positive bacteria are naturally producers of extracellular proteins that are secreted to the medium, simplifying the complex purification procedures inherent to intracellular protein accumulation
Streptomycetes are Gram-positive GRAS soil bacteria, providing a huge secretion capacity of hydrolytic enzymes together with antibiotics and signalling molecules [2] to adapt to their natural environment largely formed of insoluble polymers
Summary
The overproduction of homologous and heterologous proteins for pharmacological and industrial application requires the use of different prokaryotic and eukaryotic expression systems. The use of prokaryotic expression systems reduces the cost of the process owing to the inexpensive culture media and it has been proven to obtain high expression levels of the secreted proteins [1]. Gram-positive bacteria are naturally producers of extracellular proteins that are secreted to the medium, simplifying the complex purification procedures inherent to intracellular protein accumulation. Streptomycetes are Gram-positive GRAS (generally recognized as safe) soil bacteria, providing a huge secretion capacity of hydrolytic enzymes together with antibiotics and signalling molecules [2] to adapt to their natural environment largely formed of insoluble polymers. Streptomyces lividans, in particular, has a relatively inefficient restriction-modification system and low endogenous protease.
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