Systematic single-cell analysis of Pichia pastoris reveals secretory capacity limits productivity.

ABSTRACT: Biopharmaceuticals represent the fastest growing sector of the global pharmaceutical industry. Cost-efficient production of these biologic drugs requires a robust host organism for generating high titers of protein during fermentation. Understanding key cellular processes that limit protein production and secretion is, therefore, essential for rational strain engineering. Here, with single-cell resolution, we systematically analysed the productivity of a series of Pichia pastoris strains that produce different proteins both constitutively and inducibly. We characterized each strain by qPCR, RT-qPCR, microengraving, and imaging cytometry. We then developed a simple mathematical model describing the flux of folded protein through the ER. This combination of single-cell measurements and compu

SUBMITTER: Love KR 

PROVIDER: S-EPMC3369916 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature