TY - JOUR
T1 - Influence of oxygen concentration on the metabolism of Penicillium chrysogenum
AU - Janoska, Agnes
AU - Verheijen, Jelle J.
AU - Tang, Wenjung
AU - Lee, Queenie
AU - Sikkema, Baukje
AU - van Gulik, Walter M.
PY - 2022
Y1 - 2022
N2 - In large-scale bioreactors, there is often insufficient mixing and as a consequence, cells experience uneven substrate and oxygen levels that influence product formation. In this study, the influence of dissolved oxygen (DO) gradients on the primary and secondary metabolism of a high producing industrial strain of Penicillium chrysogenum was investigated. Within a wide range of DO concentrations, obtained under chemostat conditions, we observed different responses from P. chrysogenum: (i) no influence on growth or penicillin production (>0.025 mmol L−1); (ii) reduced penicillin production, but no growth limitation (0.013–0.025 mmol L−1); and (iii) growth and penicillin production limitations (<0.013 mmol L−1). In addition, scale down experiments were performed by oscillating the DO concentration in the bioreactor. We found that during DO oscillation, the penicillin production rate decreased below the value observed when a constant DO equal to the average oscillating DO value was used. To understand and predict the influence of oxygen levels on primary metabolism and penicillin production, we developed a black box model that was linked to a detailed kinetic model of the penicillin pathway. The model simulations represented the experimental data during the step experiments; however, during the oscillation experiments the predictions deviated, indicating the involvement of the central metabolism in penicillin production.
AB - In large-scale bioreactors, there is often insufficient mixing and as a consequence, cells experience uneven substrate and oxygen levels that influence product formation. In this study, the influence of dissolved oxygen (DO) gradients on the primary and secondary metabolism of a high producing industrial strain of Penicillium chrysogenum was investigated. Within a wide range of DO concentrations, obtained under chemostat conditions, we observed different responses from P. chrysogenum: (i) no influence on growth or penicillin production (>0.025 mmol L−1); (ii) reduced penicillin production, but no growth limitation (0.013–0.025 mmol L−1); and (iii) growth and penicillin production limitations (<0.013 mmol L−1). In addition, scale down experiments were performed by oscillating the DO concentration in the bioreactor. We found that during DO oscillation, the penicillin production rate decreased below the value observed when a constant DO equal to the average oscillating DO value was used. To understand and predict the influence of oxygen levels on primary metabolism and penicillin production, we developed a black box model that was linked to a detailed kinetic model of the penicillin pathway. The model simulations represented the experimental data during the step experiments; however, during the oscillation experiments the predictions deviated, indicating the involvement of the central metabolism in penicillin production.
KW - black box model
KW - metabolic modeling
KW - oxygen limitation
KW - penicillin pathway
KW - scale-down
UR - http://www.scopus.com/inward/record.url?scp=85127594613&partnerID=8YFLogxK
U2 - 10.1002/elsc.202100139
DO - 10.1002/elsc.202100139
M3 - Article
AN - SCOPUS:85127594613
SN - 1618-0240
VL - 23
JO - Engineering in Life Sciences
JF - Engineering in Life Sciences
IS - 1
M1 - e2100139
ER -