Unbalanced growth

R. eutropha, formerly known as Alcaligenes eutrophus, has been used for the commercial production of P(3HB-co-3HV) [72]. This bacterium grows well in a relatively inexpensive minimal medium and accumulates a large amount of P(3HB) under the unbalanced growth condition. In R. eutropha, acetyl-CoA is converted to P(3HB) by three enzymes (genes) /J-ketothiolase (phaA), aceto-acetyl-CoA reductase (phaB), and PHA synthase (phaC) [6]. 

Kinouchi T, Kataoka K, Bing SR, Nakayama H, Uejima M, Shimono K, Kuwahara T, Aki-moto S, Hiraoka I, Ohnishi Y Culture supernatants of Lactobacillus acidophilus and Bifidobacterium adolescentis repress ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug by suppressing unbalanced growth of aerobic bacteria and lipid peroxidation. Microbiol Immunol 1998 42 347-355. 

Hagiwara M, Kataoka K, Arimochi H, Kuwahara T, Ohnishi Y Role of unbalanced growth of Gram-negative bacteria in ileal ulcer formation in rats treated with a nonsteroidal anti-inflammatory drug. J Med Invest 2004 51 43-51. 

The growth of microbial populations is normally limited either by the exhaustion of available nutrients or by the accumulation of toxic products of metabolism. As a consequence, the rate of growth declines and growth eventually stops. At this point a culture is said to be in the stationary phase. The transition between the exponential phase and the stationary phase involves a period of unbalanced growth during which the various cellular components are synthesized at unequal rates. Consequently, cells in the stationary phase have a chemical composition different from that of cells in the exponential phase. 

This unbalanced growth rapidly leads to cell death if prolonged for more than a generation time (Ruekert and Mueller, 1960). Unbalanced growth will occur in any cells committed to division ( 10.4) yet blocked in one function including those maintained in colcemid for more than a few hours. Moreover, selective blocking of DNA synthesis may have effects which are not apparent until the synchronised cells are released and proceed to the next G1-phase (Firket and Mahieu, 1966 Cress and Gerner, 1977). Schindler et al. 

Lethal agents include compounds which lead to unbalanced growth by blocking DNA synthesis, e.g. fluorodeoxyuridine or cytosine arabinoside, or agents which are incorporated into DNA where they have deleterious effects, e.g. high levels of tritiated thymidine or bromodeoxyuridine which can lead to breaks in the DNA on subsequent irradiation (Thompson et al., 1970). 

Poly(jS-hydroxyalkanoates) (PHAs) are a class of poly(esters) which are synthesised by many bacteria as energy reserve and carbon source when exposed to an excess of carbon under unbalanced growth conditions [82]. The produced PHAs can account for up to 80% of the bacterium s dry weight. This has led to the biotechnological production of PHAs. Depending on the substrates provided to the bacteria, different monomers can be produced which results in different PHA (co)polymers [83]. 

In instances of unbalanced growth, secondary metabolites have been envisioned by some as shunt metabolites produced in order to reduce abnormal concentrations of normal cellular constituents. The synthesis of enzymes designed to carry out secondary metabolism permits primary metabolic enzymes to continue to function until such time as circumstances are propitious for renewed metabolic activity and growth. For example, this could be linked to the depletion of nutrients such as phosphorus or nitrogen (Bu Lock, 1980 Haslam, 1986). 

PHB is produced in R. eutropha under unbalanced growth conditions, hence a two-stage continuous culture system to be adopted. In the first stage maximum cell biomass were produced and in the second stage PHB was produced. The PHB content and productivity were 47.6% and 1.43 g/L/h, respectively. 

Under these growth conditions, the mixed culture subjected to consecutive periods of external substrate accessibility (feast period) and unavailability (famine period) generates unbalanced growth. During the excess of external caibon substrate, the growth of biomass and storage of polymer occur simultaneously. 

In a first approach to determine the mode of action of the cytostatically active clavines, incorporation studies were performed (Eich et al., 1984a). They revealed that the incorporation of PH]-thymidine into DNA is reduced in the presence of 1-propylfestuclavine. On the other hand, no influence has been determined for [ H]-uridine incorporation into RNA and PH]-phenylalanine incorporation into protein. The inhibition of the thymidine incorporation rate was only observed after a preincubation period with the clavine derivative for 24 h and was not detectable after a pretreatment period of 2h. The assumption was favoured that clavines interfere with DNA replication processes in L5178y cells rather than an unspecific effect on cell growth. This conclusion was based on the observation that all active clavines caused unbalanced growth , a property which they share with other cytostatic agents acting selectively by... 

Ralstonia species can accumulate large amounts of polyhydroxyalkanoate (PHA) under unbalanced growth conditions, where protein synthesis reactions are limited and carbon and energy are present in abundance. Ralstonia eutropha (also known as... 

Some investigators(also T. G. Mitchell, personal communication) have reported a simplification of this liquid assay procedure in which the enumeration of viable cells is replaced by the determination of the turbidity of (undiluted) treated and control cultures. Although this modification is less expensive and more rapid—results are read immediately as opposed to the requirement for overnight incubation—we have some reservations about this modification, since it is known that DNA-inhibiting agents have a propensity for unbalanced growth, i.e., a continued synthesis of RNA and proteins in the absence of DNA synthesis, which is characterized by an increase in the... 

W. G. Thilly, D. I. Arkin, T. S. Nowak, Jr., and G. N. Wogan, Maintenance of perpetual synchrony in HeLa suspension cultures Question of unbalanced growth, Biotechnol Bioeng. 

Usually, bacteria produce these granules when subjected to an unbalanced growth condition with excess carbon and simultaneous limitation of nutrient(s) such as oxygen, nitrogen, sulfur, magnesium and phosphorous. Some bacteria, however, produce them without being subjected to any kind of... 

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