Volumetric power input as a reliable parameter for scale-up from shake flask to stirred-tank bioreactor: Production of a recombinant glycoprotein by Streptomyces lividans


The filamentous morphology of Streptomyces lividans depends on the culture conditions, affecting the production, secretion and post-translational modifications of recombinant glycoproteins. In this work, the previously reported volumetric power input (P/V) in conventional (NF) and coiled (CF) shake flasks were scaled-up to a stirred bioreactor. The effects on the growth and morphology of S. lividans were analyzed, as well as, the production and O-mannosylation of the recombinant APA glycoprotein from Mycobacterium tuberculosis. Specific growth rates of 5. lividans and similar recombinant glycoprotein (rAPA) yields were observed between NF and bioreactor cultures. In addition, we have found up to seven mannose residues attached to the C-terminal of the rAPA in bioreactor cultures, one more than in NF and CF. However, at similar P/V values, morphological and kinetic differences were found. Our data indicate that P/V as scale-up criteria in the production of recombinant glycoproteins in S. lividans can be successful in some, but not all the kinetic and stoichiometric parameters, suggesting that the metabolic cell responses can be affected by aeration/hydrodynamics between bioreactor and shake flasks. © 2019, Universidad Autonoma Metropolitana Iztapalapa. All rights reserved.


Palabras clave

Morphology, Power input, Rheology, S. lividans, Scale-up, Shake flasks