Growth kinetics of P. pastoris and the toxic effect produced by methanol in solid-state (SSF) and submerged fermentation (SmF) were compared. SmF cultures of P pastoris presented moderate lysis without methanol (MetOH) after 72 h. Addition of MetOH has negligible effect on SSF system at the same conditions. MetOH addition produced lysis in both types of cultures, but nearly three times more for SmF than for SSF. Maximal biomass levels were higher (52 gL-1) for SSF as compared to SmF (42 gL-1). Microscopic observations showed smaller yeast aggregates in SmF as compared to larger aggregates in SFF. This is the first work that shows lower yeast autophagy when cultured in large aggregates within the polyurethane foam as well as lower methanol toxicity as compared to shake flask cultures. Such results could be explained in terms of possible cell to cell communication and also in terms of diffusion barriers to methanol in large yeast aggregates. This work opens the possibility of using polyurethane foam support of SSF systems as a way to increase recombinant protein production using glycerol as starting substrate and methanol as a late inducer of specific operons.