Penicillium glaucum

The method is based on the fact that certain bacteria, fungi, mould or yeast when allowed to grow in a racemic solution, assimilate or consume one of the enantiomers faster than the other. This is why the method is also known as selective assimilation or preferential decomposition. Thus Penicillium glaucum a species of green mould when allowed to grow in ammonium racemate solution consumes the d 0 tartaric acid and leaves the l form, but in a racemic lactic acid it assimilates the l form leaving behind the d form. 

Early examples of biotransformation using microbes and defined chemical substrates began to become established in the mid-nineteenth century. Pasteur noted in 1858 that when a solution of an ammonium salt of ( )-tartaric acid was fed to a culture of the mould Penicillium glaucum the (+)-tartaric acid was consumed, leaving the ( )-tartaric acid. 

By the second method Schulze and Bosshard prepared d-leucine and 1-glutamic acid, and Engel prepared d-aspartic acid. Menozzi and Appiani also separated glutamic acid by this method. In all these cases the mould Penicillium glaucum was used to effect the separation. 

From inactive cystine Neuberg and Mayer separated d-cystine, using Aspergillus niger instead of Penicillium glaucum, which gave no result with this amino acid. 

Unlike these nonspecific agents, mycophenolate mofetil (6.4) tends to be a lymphocyte-specific cytotoxic agent. Mycophenolate mofetil is a semisynthetic derivative of mycophe-nolic acid, isolated from the mold Penicillium glaucum. It inhibits both T and B lymphocyte action. Since it inhibits the enzyme inosine monophosphate dehydrogenase, which catalyses purine synthesis in lymphocytes, this agent has a more specific effect on lymphocytes than on other cell types. Mizoribine (6.5) is a closely related drug which inhibits nucleotide synthesis, preferentially in lymphocytes. 

Study of the chemical evolution of chirality started in 1809 with the discovery of Haiiy [4], who postulated from crystal cleavage observations that a crystal and each of its constituent space-filling molecules are images of each other in overall shape. Later, in 1848, Pasteur reported the different destruction rates of the dextro- and levorotatory forms of ammonium tartrate by the mold Penicillium glaucum [5]. These observations could not be explained properly at that time, but in 1874 Le Bel [6] and van t Hoff [7] independently proposed that the four valences of the carbon atom are directed toward the vertices of an atom-centered tetrahedron. This finding allowed the development of the theory of the three-dimensional structure of molecules by which the phenomenon of chirality and Pasteur s discovery were explained scientifically. 

A very old broad-spectrum compound, mycophenolic acid, first discovered in 1896 and never commercialized as an antibiotic, has recently been developed as a new immunosuppressant. Its morpholinoethylester is the commercial immunosuppressant molecule. Mycophenolic acid was isolated in the crystalline state in 1896 by Gosio and was the first pure compound to show antibiotic activity. This product of Penicillium glaucum was shown to inhibit the growth of Bacillus anthracis and was then forgotten, until rediscovered in 1913 and given its name. Before being developed into an approved immimosuppressant, mycophenolic acid was used to treat psoriasis. 

With the aid of certain micro-organisms, the inactive compounds may be decomposed into their active constituents- If, eg., the well-known Penicillium glaucum is allowed to grow in a solution of ammonium pani-mandelate. it destroys the laevo-modification while another organism, Sacckaromyces elUpsoideus, consumes the dextro-modification, and leaves the other. 

The first observation of biological enantioselectivity was made by Pasteur himself. He found, in 1858, that when solutions of racemic ammonium tartrate were fortified with organic matter (i.e., a source of microorganisms) and allowed to stand, the solution fermented and (-I-)-tartaric acid was consumed rapidly while (-)-tartaric acid was left behind unreacted. Eventually the (-)-enantiomer was also metabolized, but considerably more slowly than (-t)-tartrate [50]. In later experiments Pasteur showed that the common mold Penicillium glaucum metabolized (-I-)-tartaric acid with high enantioselectivity [51]. He correctly theorized that the enantioselective destruction of tartaric acid by microorganisms involves selective interaction of the tartrate enantiomers with a key chiral molecule within the microorganism [50, 51]. 

The influence of stereochemical differences of natural products on biological systems has already been studied by Pasteur who recognized that dextro ammonium tartrate was digested more rapidly by the fungus Penicillium glaucum than the levo isomer [56]. Ascorbic acid, also known as vitamin C, only exhibits redox activity as the (-I-)-isomer, whereas the (-)-isomer is inactive and cannot be used to treat scurvy [57]. 

The biotransformation of organic compounds by microorganisms has been an important aspect of microbiological chemistry throughout its development. In 1858 Pasteur used the fungus Penicillium glaucum to obtain L-ammonium tartrate from DL-ammonium tartrate by the selective destruction of the d-enantiomer. Today microbiological transformations are used in the commercial production of several industrial chemicals. 

Liquid culture Penicillium glaucum fowl plague... 

An active form of an acid may be obtained from the inactive variety by subjecting it to the action of certain bacteria, which destroy one form of the acid more rapidly than the other. In the case of lactic acid the dextro form may be obtained by the action of the mould called penicillium glaucum on inactive ammonium lactate. When lactic acid is made by the fermenta-... 

The third method devised by Pasteur depends on the action of certain moulds and bacteria on racemic compounds. One of the active substances is more rapidly destroyed than the other. When the mould penicillium glaucum develops in a dilute solution of racemic acid, the dextro-rotatory acid is destroyed and Z-tartaric acid is obtained. 

The differential biological activity of stereoisomers is not a new phenomenon in spite of the considerable interest over the last twenty years. Pasteur, in 1858, showed that the mold Penicillium glaucum metabolized (-l-)-tartrate more rapidly than the (—)-enantiomer and commented, the idea of the influence of the molecular asymmetry of natural organic products is introduced into physiological studies, this important characteristic being perhaps the only distinct line of demarcation which we can draw today between dead and living matter [12]. 

Bacterial attack was also shown by Pasteur to be effective in the resolution of racemic acid. Penicillium glaucum allowed to grow in a dilute solution of sodium ammonium racemate destroys the d form but, apart from being a rather wasteful process, the attack is not always completely selective. 

Pasteur, L. (1860). Note relative au Penicillium glaucum et a la dissymetrie moleculaire des produits organiques naturels. C. R. Acad. Sci. (Paris), 51, 298-9. 

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