Continuous bioproduction by decoupling growth and production

A continuous fermentation process for the production of a protein of interest or a polynucleotide of interest by a bacterial host cell, wherein the bacterial host cell comprises a nucleic acid encoding a protein from a phage which inhibits growth of said bacterial host cell, said nucleic acid under the control of a first inducible promoter, wherein said protein from phage which inhibits growth of said bacterial host cell (i) inhibits bacterial host cell RNA polymerase, (ii) inhibits host cell DNA replication, or (iii) causes host cell transcriptional shut-off, wherein said first inducible promoter promotes expression of said nucleic acid, comprising

• (a) culturing said bacterial host cell in an uninduced state with respect to the nucleic acid encoding the protein from the phage which inhibits growth of said bacterial host cell in a seed reactor;
• (b) transferring at least an amount of the bacterial host cells obtained in (a) from said seed reactor to a production reactor;
• and
• (c) culturing said bacterial host cells in said production reactor in an induced state with respect to the nucleic acid encoding the protein from the phage which inhibits growth of said bacterial host cells;
• wherein the seed reactor and production reactor is configured as an independent continuous fermentor and wherein the seed reactor and production reactor are connected with each other, wherein (a), (b), and (c) occur simultaneously during at least a portion of the continuous fermentation process, and wherein the seed reactor and the production reactor are configured as linked chemostats or turbidostats.