Cutting Costs in Serum-Free FGF2 Processing With Recycled Media
Reusing spent culture media in an L. lactis cell fermentation model streamlines continuous bioprocessing and cuts costs for FGF2 production, making serum-free production increasingly cost-effective and productive. The post Cutting Costs in Serum-Free FGF2 Processing With Recycled Media appeared first on GEN - Genetic Engineering and Biotechnology News .
Producing fibroblast growth factor 2 (FGF2) using recycled spent cell culture media from Lactococcus lactis production can reduce costs while keeping high production levels, according to research from Singapore's Agency for Science, Technology and Research (A*STAR). This method may eventually replace the large amounts of fetal bovine serum typically used.
"This project establishes a high-value circular manufacturing framework by repurposing nutrient-rich spent media side-streams generated during biopharmaceutical cell culture as low-cost feedstock for precision microbial fermentation," explained Dave Ow, PhD, a principal scientist and group leader at A*STAR's Bioprocessing Technology Institute (BTI).
The team, led by Ow and Prashant Mainali, PhD, a bioprocess scientist at BTI, A*STAR, selected L. lactis as the production cell due to its fast doubling time of 35-60 minutes and ability to secrete recombinant proteins, reducing the need for extensive downstream purification. Reusing and fortifying the spent media lowers the cost of fresh media formulation, increasing productivity and decreasing the cost per gram of FGF2.
Moreover, they adapted this approach for continuous manufacturing processes for both intracellular and secreted FGF2 production, optimizing conditions and integrating models with downstream purification.
The optimal conditions for this process are 10 g/L glucose, 35°C temperature, and 100 ng/mL nisin concentration. The glucose-temperature interaction was statistically significant, while the glucose-nisin interaction was not. Balancing tradeoffs, such as minimizing nutrient loss or maximizing FGF2 concentration, is crucial. The team used a chemostat process to simulate process outcomes under varying conditions, accurately predicting cell, glucose, lactate, and intracellular FGF2 concentrations.
However, the model underpredicted FGF2 concentrations. Integrating depth filtration and crossflow filtration into the chemostat process, similar to those used in Escherichia coli, proved feasible.
The FGF2 produced was used directly to supplement cell cultures, showing comparable growth to cells cultured with commercially available FGF2 and fetal bovine serum (FBS)-supplemented media in Anguilla japonica (Japanese eel) cells. The researchers concluded that fortified spent cell culture media can support L. lactis growth and FGF2 secretion, simplifying downstream purification and making spent media reuse both cost-effective and environmentally friendly.
This approach could help reduce FGF2 costs while overcoming one of the main economic barriers to serum-free media, with biopharma manufacturers showing interest in implementing similar upcycling strategies in their production processes.
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