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Investigation of the physiological response to oxygen limited process conditions of Pichia pastoris Mut+ strain using a two-compartment scale-down system

Paper ID Volume ID Publish Year Pages File Format Full-Text
20772 43190 2013 9 PDF Available
Title
Investigation of the physiological response to oxygen limited process conditions of Pichia pastoris Mut+ strain using a two-compartment scale-down system
Abstract

•Scale-up relevant physiological responses to oxygen limited process conditions.•Methodological novelty: combining scale-down setup with multivariate techniques.•Differentiation of physiological key parameters with only on-line data.•Valuable process development tool for accelerating host strain characterization.•Scale-down tool for verifying CFD simulations of large-scale bioreactors.

Inhomogeneities in production-scale bioreactors influence microbial growth and product quality due to insufficient mixing and mass transfer. For this reason, lots of efforts are being made to investigate the effects of gradients that impose stress in large-scale reactors in laboratory scale. We have implemented a scale-down model which allows separating a homogeneous part, a stirred tank reactor (STR), and a plug flow reactor (PFR) which mimics the inhomogeneous regimes of the large-scale fermenters. This scale-down model shows solutions to trigger oxygen limited conditions in the PFR part of the scale-down setup for physiological analysis. The goal of the study was to investigate the scale-up relevant physiological responses of Pichia pastoris strain to oxygen limited process conditions in the above mentioned two-compartment bioreactor setup. Experimental results with non-induced cultures show that the specific growth rate significantly decreased with increasing the exposure time to oxygen limitation. In parallel more by-products were produced. Examining physiological scalable key parameters, multivariate data analyses solely using on-line data revealed that different exposures to the oxygen limitation significantly affected the culture performance. This work with the small scale-downs setup reflects new approaches for a valuable process development tool for accelerating strain characterization or for verifying CFD simulations of large-scale bioreactors. As a novel methodological achievement, the combination of the two-compartment scale-down system with the proposed multivariate techniques of solely using on-line data is a valuable tool for recognition of stress effects on the culture performance for physiological bioprocess scale-up issues.

Keywords
Scale-down; Two-compartment reactor; Pichia pastoris; Stress response; Oxygen limitation
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Investigation of the physiological response to oxygen limited process conditions of Pichia pastoris Mut+ strain using a two-compartment scale-down system
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 116, Issue 3, September 2013, Pages 371–379
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us