TY  - JOUR
AU  - Habicher, Tobias
AU  - Rauls, Edward K. A.
AU  - Egidi, Franziska
AU  - Keil, Timm
AU  - Klein, Tobias
AU  - Daub, Andreas
AU  - Büchs, Jochen
TI  - Establishing a Fed‐Batch Process for Protease Expression with Bacillus licheniformis in Polymer‐Based Controlled‐Release Microtiter Plates
JO  - Biotechnology journal
VL  - 15
IS  - 2
SN  - 1860-7314
CY  - Weinheim
PB  - Wiley-VCH
M1  - FZJ-2020-01677
SP  - 1900088 -
PY  - 2020
AB  - Introducing fed‐batch mode in early stages of development projects is crucial for establishing comparable conditions to industrial fed‐batch fermentation processes. Therefore, cost efficient and easy to use small‐scale fed‐batch systems that can be integrated into existing laboratory equipment and workflows are required. Recently, a novel polymer‐based controlled‐release fed‐batch microtiter plate is described. In this work, the polymer‐based controlled‐release fed‐batch microtiter plate is used to investigate fed‐batch cultivations of a protease producing Bacillus licheniformis culture. Therefore, the oxygen transfer rate (OTR) is online‐monitored within each well of the polymer‐based controlled‐release fed‐batch microtiter plate using a µRAMOS device. Cultivations in five individual polymer‐based controlled‐release fed‐batch microtiter plates of two production lots show good reproducibility with a mean coefficient of variation of 9.2%. Decreasing initial biomass concentrations prolongs batch phase while simultaneously postponing the fed‐batch phase. The initial liquid filling volume affects the volumetric release rate, which is directly translated in different OTR levels of the fed‐batch phase. An increasing initial osmotic pressure within the mineral medium decreases both glucose release and protease yield. With the volumetric glucose release rate as scale‐up criterion, microtiter plate‐ and shake flask‐based fed‐batch cultivations are highly comparable. On basis of the small‐scale fed‐batch cultivations, a mechanistic model is established and validated. Model‐based simulations coincide well with the experimentally acquired data.
LB  - PUB:(DE-HGF)16
C6  - pmid:31471944
UR  - <Go to ISI:>//WOS:000511444500003
DO  - DOI:10.1002/biot.201900088
UR  - https://juser.fz-juelich.de/record/874872
ER  -