When seeking to produce a toxic protein as a primary product, Phenotypeca’s combination of known rational engineering, a stable but exchangeable 2-micron expression vector, and breeding for optimising diversity and subsequent QTL analysis has a proven record of improving fermentation and purification processes, leading to commercially viable net yields. Specifically, genetic and metabolic engineering are powerful tools in Phenotypeca’s capacity for increasing robustness. For example, the overexpression of stress response and/or anti-apoptotic pathways can confer tolerance and prevent cell death upon expression of toxic proteins. Expression level can also be optimised through the use of inducible promotors which enable controlled expression of toxic proteins. This approach of targeted engineering is combined with breeding and QTL analysis to select the most robust strains for the production of a toxic primary product. Finally, media optimisation (including the use of protective agents) further supports the selected strains.