Engineering of Biological Processes Lecture 4: Production kinetics. Mark Riley, Associate Professor Department of Ag and Biosystems Engineering The University of Arizona, Tucson, AZ 2007. Objectives: Lecture 4. Investigate production kinetics and limiting factors.
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Mark Riley, Associate Professor
Department of Ag and Biosystems Engineering
The University of Arizona, Tucson, AZ
Biotechnol Prog. 1990 May-Jun;6(3):231-6. Suzuki E, Ollis DF.
Generalized production equation
The above is a gross over-simplification of production rates.
Non-growth assoc.Kinetic expressions require growth-associated and maintenance-associated production
YP/X is the theoretical yield of product from biomass, mp is the specific rate of product formation due to maintenance, and x is biomass concentration.
Result = Y’p/x is higher than anticipated based on growth alone
Limited by the depletion of a resource (nutrient, space, oxygen).
Assumes substrate metabolism
used only to make
product (no x or ms)Substrate uptake
Substrate uptake metabolism
Result = rs is higher than anticipated based on only growth and product formation
If there is no product generated (q metabolismp=0)
Plot (1/Y’x/s) vs. 1/m – slope = ms
rp decreases Y’x/s
Cancel out “X” ’s metabolism
Yx/s * Yp/x = Yp/s
Growth assoc. metabolism
Non-growth assoc.Maximize production
"Growth, metabolic, and antibody production kinetics of hybridoma cell culture: Effects of serum concentration, dissolved oxygen, and pH in a batch reactor."
The effects of serum, dissolved oxygen (DO) concentration, and medium pH on hybridoma cell growth, viability, cell density, carbohydrate and amino acid metabolism, respiration and energy production rates, and antibody production rates were studied.
Cell growth was enhanced and cell death was decreased by increasing the serum level. The growth rates followed a Monod-type model with serum being the limiting component.
Specific glucose, glutamine, and oxygen uptake rates and specific lactate and ammonia production rates did not change with serum concentrations. Amino acid metabolism was slightly influenced by the serum level.
Oxidative phosphorylation accounted for about 60% of total energy production. This contribution, however, increased at low pH values to 76%.
The specific antibody production rate was not growth associated and was independent of serum and DO concentrations. A 2-fold increase in specific antibody production rates was observed at pH values below 7.2.
Higher concentrations of antibody were obtained at high serum levels, between 20% and 40% DO, and at pH 7.20 due to higher viable cell numbers obtained.
↑ S, ↑ P
↑ mmax, ↓ P
↓ mmax, ↓ P
↑Y'p/s, ↑ P
↓Y'x/s, ↑ P