towards the synthesis of a simple cell

Darwinian chemistry: towards the synthesis of a simple ..

Darwinian chemistry: towards the synthesis of a simple cell

The upper and lower panels give estimates calculated by the twomethods, and the agreement between them is very good. The probability of spontaneoussynthesis of the smallest cell (or virus) turns out to be unimaginably small in anequilibrium situation. To obtain the probability that a cell (or other structure) wouldoccur spontaneously once in the history of the universe, P1 (max) is multipliedby 10134. This factor is obtained by allowing all the atoms in the knownuniverse (about 10100) to react at the maximum rate of chemical processes(about 1016 sec-1) for a time of 1010 years. However,this factor is negligible in comparison with probabilities as small as 10-1011and leaves them unchanged. When numbers as infinitesimally small as P1 (max)are encountered, no amount of ordinary manipulation or arguing about the age of theuniverse or its size can suffice to make it plausible that such a synthesis could haveoccurred in an equilibrium system (11). The same type of calculation can also be used toestimate the maximum-sized macromolecule which might be expected as a result of randomsynthesis. In a mixture the size of the universe, reacting for over a billion years, thisturns out to be only a small polypeptide (11).
These calculations illustrate the immense amount of organization thatwent into the production of the first living system. Equilibrium thermodynamics, likestatistical mechanics, points unmistakably to the conclusion that purely random chemicalcombinations cannot account for the origin of life. In fact this idea has now been almostwholly abandoned (except in elementary texts). It is recognised that some "principleof organization," "selection factor" or "design mechanism" mustoperate, or have operated, in the past. Crick believes that the necessary organization wasthe outcome of Darwin's principle of natural selection (3), Morowitz (11), and others,consider that non-equilibrium thermodynamics can supply the answer, Cairns-Smith (8)voices the opinion that self-organization is an inherent property of certain molecularaggregates and macromolecules, Elsasser (12) and Polanyi (13) champion the view that someaspects of biological systems cannot be accounted for in terms of the presently known lawsof physics. Before turning to a consideration of these theories of self-organization, wewill examine the second problem theoretical physics poses in the field of livingstructures.

The total synthesis of a simple cell is in many ways the ultimate challenge in synthetic biology

Outlined eight years ago in a visionary article by Szostak et al

However, recent progress in nucleic acid chemistry, directed evolution and membrane biophysics have brought the prospect of a simple synthetic cell with life-like properties such as growth, division, heredity and evolution within reach.


Here, the directed evolution of protein is discussed through the effect of compartment size on protein function. Nature contains living prokaryotes with cell sizes that range from 0.02fL to 400fL []. The lower limit of the cell size is determined by the catalytic efficiency of enzymes, protein synthesis machinery, and machinery to cope with sudden environmental changes []. Under this theory, smaller cells could be generated if the enzyme catalytic efficiency was greater. Naturally occurring proteins have evolved in the cell through Darwinian selection. However, directed evolution of protein has never been discussed regarding compartment size because conventional microcompartments (emulsions) have been unsuitable for this purpose. Of the gene screening techniques for directed evolution of proteins, liposome-based IVC is the most promising technique for studying how compartment size influences protein evolution because the internal aqueous phase volume of the liposome is accurately evaluated by FACS measurement. A molecular evolution system using liposome-based IVC is an experimental approach for simulating the evolutionary process of protein function in a certain cell size.

ChemInform Abstract: TOTAL SYNTHESIS OF ..