Mimicking Marine Conditions to Improve Prodigiosin Yields in Bioreactor

Prodigiosin is a red bacterial pigment with great potential as a natural dye and drug precursor, while presenting several pharmacological properties, including antimicrobial and anticancer activities. Its commercialization for biomedical applications, however, remains scarce. The major limitations are related to the lack of efficient bioprocesses and scaling up from laboratory to production. In the present work, the upstream process for prodigiosin production was developed using a marine Serratia rubidaea isolated from a sample collected near a shallow-water hydrothermal vent. The yield of product per biomass was found to be influenced by the cell concentration in the inoculum. The system was scaled up to 2 L stirred tank reactors with two different vessel geometries. It was shown that the vessel geometry and a cascade control mode for regulating the dissolved oxygen concentration influenced the volumetric oxygen mass transfer coefficient (k_La) and thus prodigiosin production. To improve product yields, strategies to mimic the aeration conditions found at the sampling site were tested. When the inoculum was grown for 5 h at 200 rpm and for 19 h at 25 rpm, which significantly decreased the oxygen available, the cells produced 588.2 mg_product/g_biomass, corresponding to a production of 1066.2 mg of prodigiosin in 24 h and a productivity of 36.1 mg_product/(L.h). This is a 3.7-fold increase in prodigiosin yield and a 4.5-fold increase in productivity in relation to when no particular strategy was promoted. Additionally, it was shown that lipid analysis and flow cytometry may be used as reliable at-line analytical tools, allowing the monitoring of cell condition and prodigiosin production during fermentation.