Scale-down assessment of the sensitivity of Yarrowia lipolytica to oxygen transfer and foam management in bioreactors: investigation of the underlying physiological mechanisms

A scale-down investigation of the impact of local dissolved oxygen limitation on lipase production by Y. lipolytica has been performed. One of the major issues encountered during this kind of process is foam formation, requiring a reduction of the overall oxygen transfer efficiency of the system in order to keep antifoam consumption to a reasonable level. A regulation strategy involving oxygen enrichment of the air flow through the reactor has allowed this issue to be partly overcome. For a second time, the scale dependency of the process operated with air enrichment has been investigated by a combination of scale-down and pilot-scale cultivation tests. The scale-down apparatus considered in this work comprised a well-mixed part connected to a plug-flow part subjected to dissolved oxygen limitation. Surprisingly, foaming intensity was greatly reduced in the case of the test performed in scale-down reactors (SDRs) while maintaining the same stirring and aeration intensities in the stirred part of the reactor. For mean residence time of 100 s in the recycle loop of the reactor, foam formation was significantly reduced while cell growth and lipase production were both unaltered. When the residence time in the recycle loop was raised to 200 s, the foam phenomena was also reduced, but the lipase yield was altered as well as lip2 gene transcription and translation as shown by real-time quantitative polymerase chain reaction (RT-qPCR) and reporter gene activity, respectively. Our results clearly show the importance of primarily taking into account cell physiology for the scaling-up procedure.