New case study: Clone Selection in Pichia pastoris

What happens when clone ranking changes as cultivation conditions become more process-relevant?

Our new case study “Process-Relevant Clone Selection in a Typical Pichia pastoris Strain Development Workflow” shows why choosing several promising clones for bioprocess evaluation strengthens final production strain selection.

Microscale screening identifies the most promising candidate pool. Process-relevant confirmation helps determine which candidate is best suited as the production strain.

High-throughput clone screening provides a reliable basis for identifying a strong pool of production strain candidates. But selecting only the single top-ranked clone can still mean overlooking the strain that performs best under actual fermentation conditions.

Key findings

  • Clone ranking changed under process-relevant conditions. The initial screening winner showed impaired biomass formation during methanol-induced microbioreactor cultivation.
  • The difference was confirmed in 1 L bioreactors.
  • Several promising clones should be advanced rather than relying on a single top-ranked candidate; microbioreactor cultivation can provide an efficient intermediate selection step.
  • The best production strain reached 6.6 g/L VHH, compared with 1.6 g/L for the benchmark strain, a more than fourfold increase in titer. 
     

Read the full case study written by Aid Atlic, Head of Fermentation Process Development.