Integrated single-cell analysis shows Pichia pastoris secretes protein stochastically.
The production of heterologous proteins by secretion from cellular hosts is an important determinant for the cost of biotherapeutics. A single-cell analytical method called microengraving was used to examine the heterogeneity in secretion by the methylotrophic yeast Pichia pastoris. We show that constitutive secretion of a human Fc fragment by P. pastoris is not cell-cycle dependent, but rather fluctuates between states of high and low productivity in a stochastic manner.
Love
Kerry Routenberg
KR
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA. george.miesegaes@fda.hhs.gov
Panagiotou
Vasiliki
V
Jiang
Bo
B
Stadheim
Terrance A
TA
Love
J Christopher
JC
D018929:Cell Culture Techniques / Q000295:instrumentation*; D003198:Computer Simulation; D004867:Equipment Design; D020869:Gene Expression Profiling / Q000295:instrumentation*; D008954:Models, Biological; D010843:Pichia / Q000502:physiology*; D040081:Protein Array Analysis / Q000295:instrumentation*; D011994:Recombinant Proteins / Q000378:metabolism*; D013269:Stochastic Processes; D018511:Systems Integration
D011994:Recombinant Proteins