Suicide containment systems

Contreras, A., Molin, S. Ramos, J. L. (1991). Conditional-suicide containment system for bacteria which mineralize aromatics. Applied and Environmental Microbiology, 57,1504-8. 

Metabolites that are less reactive than suicide inhibitors may impact more distant enzymes, within the same cell, adjacent cells, or even in other tissues and organs, far removed from the original site of primary metabolism. For example, organopho-sphates (OPs), an ingredient in many pesticides, are metabolized by hepatic CYPs to intermediates, which, when transported to the nervous system, inhibit esterases that are critical for neural function. Acetylcholinesterase (AChE) catalyzes the hydrolysis of the ester bond in the neurotransmitter, acetylcholine, allowing choline to be recycled by the presynaptic neurons. If AChE is not effectively hydrolyzed by AChE in this manner, it builds up in the synapse and causes hyperexcitation of the postsynaptic receptors. The metabolites of certain insecticides, such as the phos-phorothionates (e.g., parathion and malathion) inhibit AChE-mediated hydrolysis. Phosphorothionates contain a sulfur atom that is double-bonded to the central phosphorus. However, in a CYP-catalyzed desulfuration reaction, the S atom is... 

Conditional suicide system for containment of bacteria and plasmids. BiotTechnology, 5, 1315-18. 

Enzymes containing pyridoxal phosphate are prime targets for suicide inhibition because the chemistry is so naturally suitable. As discussed in Chapter 2, section C2, the pyridoxal ring acts as an electron sink that facilitates the formation of carbanions and also forms part of an extended system of conjugated double bonds. For example, vinyl glycine, CH2=CHCH(NH3+)C02, condenses with the pyridoxal phosphate of aspartate aminotransferase to form a Schiff base, as described in Chapter 2, equation 2.42.19 The a proton may be abstracted (as in equation 2.43) so that the isomerization shown in equation 9.13 readily occurs. 

Madin, K., Sawasaki, T., Ogasawara, T., and Endo, Y. (2000) A highly efficient and robust cell-free protein synthesis system prepared from wheat embiyos plants apparently contain a suicide system directed at ribosomes. Proc. Natl. Acad. Sci. USA 97, 559-564. 

Figure 4. A suicide gene expression containment model system. PI - Promoter of Inducible operon. VP2 - Viral promoter 1. VP2 - Viral promoter 2.

Phosphorus is an essential mineral element. Phosphorus homeostasis in the body is controlled by hormonal and renal control systems. Phosphorus intoxication from excessive consumption in food is not known. Toxic exposures have been reported to occur from its industrial use or from suicidal ingestion of phosphorus-containing materials. Phosphorus is highly toxic to humans and animals. The acute lethal dose in humans is lmgkg . ... 

The vector also contains the cis elements needed for packaging in HIV-1 particles, and with two genetic systems to obtain an effective and selective ehmination of the latently infected cells, without altering the normal function of the transduced uninfected cells. In summary, the genetic construction contains an externally inducible system that promotes the expression of any latent HIV-1 provirus without affecting the cell cycle state, whilst a second genetic system included in the vector allows the detection of an essential viral protein and expression of a suicide gene in response to the viral protein (Fig. 7.4). 

The term mole was first introduced by Wilhelm Ostwald in 1901. It is derived from the Latin for mass, hump, or pile (the term molecule, introduced by Pierre Gassendh in the early seventeenth century has the same root presumably it means a mass of atoms). Specifically, Ostwald used the term to represent the formula weight of a substance in grams 36.5 g of HCl is one mole. The formal definition of the mole adopted by the Fourteenth Conference Generale des Poids et Mesures in 1971 is the amount of a substance of a system that contains as many elementary entities as there are atoms in 0.012 kilograms of carbon-12. The rich irony is that Ostwald fiercely resisted the atomic concept at the time Boltzmann committed suicide in 1906 but his mole is now defined explicitly in terms of atoms. 

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