Parametric continuous feed stream design to fine-tune fed-batch bioreactor performance: recombinant human growth hormone production in Bacillus subtilis

BACKGROUND: Design principles of a fed-batch bioreactor system to fine-tune bioreactor performance by increasing production and productivity are investigated. To enhance the production and productivity in fed-batch fermentation of recombinant human growth hormone (rhGH) by Bacillus subtilis, this work develops a continuous feed stream (CFS) design method with the parameters, cultivation time to switch batch-to fed-batch operation, so called transition time, t(T), and specific growth rate, mu

Methanol feeding strategy design enhances recombinant human growth hormone production by Pichia pastoris

BACKGROUND: The effects of designed methanol and co-substrate feeding strategies on fed-batch recombinant human growth hormone (rhGH) production by Pichia pastoris hGH-Mut(+) were investigated

Recombinant protein production in Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter: From carbon source metabolism to bioreactor operation parameters

The yeast Pichia (Komagataella) pastoris has become a potential host system for recombinant protein (r-protein) production. Several strong inducible and constitutive promoters have been identified in P. pastoris which make the host ideal in r-protein expressions. The constitutive promoter of the glyceraldehyde-3-phosphate dehydrogenase gene. P-GAp, is promising as its use offers the advantage of associating product quantity to growth which can be optimized by a well-designed feeding strategy so long as the product itself is not toxic to the host. In this article, carbon source metabolism and the central carbon pathways of P. pastoris are reviewed. After comparing P-GAp with the available promoters of P. pastoris, the bioreactor operation parameters and bioreactor operation strategies are analyzed for r-protein production under P-GAp by focusing on response of the cells, final product concentration, yield, and productivity. The overview of the subject reveals the requirement for in-depth information on the overall regulation of P. pastoris metabolism that can enable fine-tuning bioreactor operation parameters in relation with the physiology of the microorganism in order to develop new strategies for the enhanced r-protein production