The success of Pichia pastoris as a heterologous expression system lies predominantly in the impressive yields that
can be achieved due to high volumetric productivity. However, low specific productivity still inhibits the potential
success of this platform. Multi-(gene) copy clones are potentially a quick and convenient method to increase
recombinant protein titer, yet they are not without their pitfalls. It has been more than twenty years since the first
reported use of multi-copy clones and it is still an active area of research to find the fastest and most efficient
method for generating these strains. It has also become apparent that there is not always a linear correlation
between copy number and protein titer, leading to in-depth investigations into how to minimize the negative
impact of secretory stress and achieve clonal stability.