A process understanding approach was applied to a late-stage recombinant protein vaccine produced in Saccharomyces cerevisiae. The manufacturing process consists of glucose batch and glucose-limited exponential fed-batch growth phases and a galactose-induced protein production phase. Physiological characterization was combined with transcriptomic and extracellular metabolomic analyses to elucidate the observed lack of galactose metabolism of the strain. When grown on various carbon sources, including glucose, galactose, and ethanol, the strain only grew well on glucose. During continuous cultivation, the strain washed out at a dilution rate of 0.2 h-1, which is significantly lower than the batch glucose maximum specific growth rate (0.29 h-1). Transcriptome analysis revealed no dysfunction in transcription of any of the major galactose metabolic pathway genes. This work demonstrated the value of a process understanding approach, which can be leveraged for improvements to existing manufacturing-scale processes or de novo process development programs.

Process understanding approach for a late-stage recombinant protein vaccine produced in <i>Saccharomyces cerevisiae</i>

243rd National Meeting (2012)

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Process understanding approach for a late-stage recombinant protein vaccine produced in Saccharomyces cerevisiae