Scalable fermentation process

A process for expression of a recombinant capsid protein of a RNA bacteriophage being capable of forming a virus-like particle (VLP) by self-assembly, wherein said RNA bacteriophage is RNA bacteriophage Qβ, and wherein said recombinant capsid protein comprises SEQ ID NO:5, said process comprising:

• a.) introducing an expression plasmid into a bacterial host, wherein said expression plasmid comprises an expression construct, wherein said expression construct comprises (i) a first nucleotide sequence encoding said recombinant capsid protein, or mutant or fragment thereof, and (ii) a promoter being inducible by lactose;
• b.) initiating a growth phase by cultivating said bacterial host in a medium comprising a major carbon source;
• wherein said cultivating initiates a batch phase during said growth phase, wherein said cultivating is performed in batch culture and under conditions under which said promoter is repressed by lacI, wherein said lacI is overexpressed by said bacterial host, and wherein no feeding of said batch culture is performed during said cultivating;
• c.) ending said batch phase and initiating a feed phase during said growth phase by feeding said batch culture with said major carbon source;
• wherein said feeding of said batch culture is performed with a flow rate, wherein said flow rate increases with an exponential coefficient μ, and
• d.) ending said growth phase and initiating a production phase by inducing said promoter with an inducer, wherein said feeding of said batch culture with said major carbon source is continued;
• and
• wherein during said steps (b.), (c.) and (d.) no removal of medium, except for analytical purposes, takes place leading to an increased density of said bacterial host in said medium.