Non growth associated

Cyclotides, circular mini-proteins bearing a cystine knot motif, are produced by plants as part of their defense mechanism. These cyclic proteins are thermostable and were recently shown to disrupt the membrane of human lymphoma cell line HeLa, causing cellular leakage. The combined approach growth- and non-growth-associated pattern provided the accumulation of 370-mg cyclotide kalata Bl/gdw within Oldenlandia affinis cells in culture. " ... 

The metabolism of an organism is in most cases related to growth and reproduction and it is then termed primary metabolism. In many cases, however, metabolism can be uncoupled from growth by limiting some nutrient or by environmental control. This non-growth associated metabolism of an organism is called secondary metabolism. 

Microbial metabolites contribute to the list of products as well, such as with fermentations to such major products as ethanol, acetic acid, n-butanol, or lactic acid key growth factors such as amino acids or vitamins or pharmacologically active compounds such as antibiotics, steroids, or alkaloids. Pharmacologically active agents are generally catagorized as secondary metabolites, which most often implies production in the stationary (non-growth-associated) phase of fermentation (Chap-... 

The maintenance coefficient can explain the non-growth associated substrate consumption for energy production, an energy that supports transmembrane ions gradient, motility, among other functions. 

Profile for growth and product synthesis according to different production models (A) growth associated production B) growth partially associated production, and C) non-growth associated production. 

Some models utilize the concept of Luedeking and Piret (1959) for growth associated and/or non-growth associated production (Equations 65 to 67). However, in some circumstances, the best fit occurs when the specific death rate kj is considered, instead of the specific growth rate px (Equations 68, 70 and 71) (Linardos et al., 1991 Zeng, 1996a, 1996b). This statement follows the observation that antibody production increases when cells are under conditions of stress. 

The aggregation of cells in suspension culture leads to a heterogeneous population that confound the analysis and operations of the reactor types mentioned above in many cases. For non-growth associated products, immobilization of cells provides a... 

Ethanol production is essentially redox neutral however metabolism associated with biomass production generates nett NADH, which is oxidised largely by glycerol production. Other important NADH oxidising reactions with flavour implications are the production of 2,3-butanediol, L-malic acid and succinic add. When glycerol production is stimulated by non-growth associated reactions (i.e. osmotic stress) NAD+ reduction occurs by other reactions including the oxidation of acetaldehyde to acetic acid... 

For most cell lines it is found to increase with the specific growth rate. Thus the specific rates of lactate production can be expressed as a function of p by Equation 4.3.4, which contains two parameters the non-growth-associated specific lactate production rate, mLac (mmol lactate 10 cells h ), and the lactate to biomass stoichiometric yield, (mmol lactate 10 cells). A similar expression is often applicable to the specific rate of ammonia production (Equation 4.3.6) and antibody secretion (Equation 4.3.7). 

Each of the five linear relationships between the specific rate of cell metabolism and the specific rate of cell growth contains two parameters a stoichiometric coefficient Y and a non-growth-associated specific rate m. From the plots shown in Figure 4.3.3 one can thus evaluate the values of ten of the parameters as the slope of the straight lines and their intercept with the y-axis. The determined values are reported in Table 4.3.2. 

According to previous kinetic studies, for many cells the production of antibody is not simply growth associated as assumed in the model presented. One may observe a specific protein production rate independent of cellular growth rate. Under these conditions a non-growth-associated type of rate expression has to be selected for protein production. 

Non-growth-associated specific rates (mmol or mg 10" cells h ) Monoclonal antibody concentration (mg 1" )... 

Sato and Yoshizawa [119] modeled the production of ethanol, a catabolic end product, during SSF of Saccharomyces cerevisiae. The rate of ethanol production was assumed to be directly proportional to the rate of carbon dioxide formation, which had both growth and non-growth associated terms as shown in Eq. (18). The non-growth associated term represented maintenance metabolism and the non-growth associated rate constant was assiuned to decrease exponentially as the ethanol concentration increased, in order to describe the inhibitory effect of ethanol on its own production. 

There are two types of fed-batch production one results in a growth-associated product and the second results in a non-growth associated product. Cupriavidus necator has been reported to produce a nongrowth-associated product. In this type of production, there is a microbial growth phase followed by a PHA production phase... 

The difficult modeling of non-growth-associated product formation has been attempted by introducing time dependence. Shu (1961) proposed an empirical approach... 

Non-growth-associated production formation is the most difficult type to model Another simple and yet plausible equation for such modeling involves the concept of the maturation time (Brown and Vass, 1973). The maturation time is taken as a kind of time delay between growth and production formation this is shown in Fig. 5.45a. The equation is either... 

Figure 6.7. Growth-associated (a) and non-growth-associated (b) product formation, growth, and productivity D-p inCSTR operation without Pinhibition. Ypjx = 0.5 and...

Adapts quite well to production of secondary metabolites that may include non-growth-associated products like recombinant proteins. 

In designing a bioreactor, the mass balance of products is usually required. The simplest way to give a kinetic expression for the product generation is to link this quantity to the rate of substrate consumption or to the behavior of the cell population. Two kinds of product generation can occur one is associated with the growth of the cells, the other one is non-growth associated. In the former mechanism, the production rate is proportional to... 

Non growth-associated product formation in the stationary phase... 

After nutrients and substrate begin to diminish, cell growth decelerates and enters a period of no apparent growth. This phase is known as the stationary phase. In the stationary phase, the rate of growth equals the rate of cell death and no net change in cell mass concentration occurs. Fermentation products produced during the stationary phase are known as non-growth associated products. 

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