Penicillium molds

The nature of the penicillin derivatives accessible by this "feeding" route was severely limited by the fact that the acylat-ing enzyme of the Penicillium molds would accept only those carboxylic acids which bore at least some resemblance to its natural substrates. A breakthrough in this field was achieved by the finding that rigid exclusion of all possible side-chain substrate from the culture medium afforded 6-APA as the main fermentation... 

For example, molds and bacteria produce substances that prevent other organisms from growing in their vicinity. The famous Penicillium mold led, via the pharmaceutical industry, to penicillin. However, penicillin was not stable in the acidic environment of the stomach, and so compounds were synthesized by chemists to produce a range of useful semisynthetic penicillin analogues. An example of the use of analogues to develop new antibacterial antibiotics is provided in Chapter II-14, on the development of moxifloxacin. 

The Penicillium mold has another important use, namely the production of antibiotics. Two species have been used for the production of penicillin, the first antibiotic to be discovered Penicillium notatum and Penicillium chrysogenum. The Penicillium species can grow on different substrates, such as plants, cloth, leather, paper, wood, tree bark, cork, animal dung, carcasses, ink, syrup, seeds, and virtually any other item that is organic. 

J course of human history He noticed that the growing Penicillium mold... 

Fleming realized that the Penicillium mold must be producing a chemical that killed the Staphylococcus bacteria, and he spent several years trying to isolate the substance, Finally, in 1939, the Australian pathologist Howard Florey and the German refugee Ernst Chain man-... 

The structure of this antibiotic was elucidated in 1945. The most notable feature of this structure is the four-membered p-lactam ring. This unusual feature is key to the antibacterial function of penicillin, as noted earlier (p. 222), Three steps were crucial to fully capitalize on Fleming s discovery. First, an industrial process was developed for the production of penicillin from Penicillium mold on a large scale. Second, penicillin and penicillin derivatives... 

Microorganisms such as molds (e.g., penicillium mold) and bacteria were found to excrete toxic substances prohibiting the growth of other organisms in close proximity. Similarly, certain plants have been known to possess medicinal properties for centuries, with willow bark and leaves being one famous example. 

Penicillin was discovered accidentally in 1929 when Sir Alexander Fleming observed bacterial cultures contaminated with a mold that inhibited bacterial growth. The antibiotic penicillin was subsequently isolated from cultures of the Penicillium mold. In 1938 two other British scientists, Howard... 

Tracking down the source of contamination is not difficult, For instance, the photographs below show two media filled petri dishes contaminated with a Penicillium mold. Although the contaminant may be the same, the source of contamination is likely to be quite different. The plate in Fig. 

Figure 174 Penicillium mold near to transferred wedge of mushroom mycelium.

Figure 175 Penicillium mold along outer periphery of petri dish.

The penicillins and cephalosporins, collectively known as beta-lactam antibiotics, are among the most widely used and valuable antibiotics currently available. Ben-zylpenicilhn (penicillin G) and phenoxymethylpenicillin (penicillin V) are derived from Penicillium molds by fermentation, while half-synthetic penicillins are derived by chemical modification of the penicillin nucleus, 6-aminopenicillanic acid (6-APA), itself obtained either by splitting the side chain from benzylpenicillin through an enzymatic process or via a chemical deacylation reaction. 

Those drugs that come from natural sources, either directly or after chemical modification, are usually chiral and are generally found only as a single enantiomer rather than as a racemate. Penicillin V, for example, an antibiotic isolated from the Penicillium mold, has the 2S,5R,6R configuration. Its... 

Penicillin V is a semisynthetic penicillin in clinical use. It is not a naturally occurring penicillin, but it is also not a true synthetic penicillin because chemists do not synthesize it. The Penicillium mold synthesizes it after being fed 2-phenoxyethanol, the compound needed for the R group. 

The key developments leading to the pool of information collected in these earlier works is outlined in an introduction to this compendium by Professor Sir Edward Abraham, a dominant figure throughout the 40 years since the first demonstration of therapeutic effectiveness of a crude fermentation product from a Penicillium mold. Sir Edward s vivid documentation of these events sets the stage for the description of the vast expansion of knowledge that occurred from 1971 through 1981 with regard to the numbers of new p-lactam structures that are potent broad-spectrum antibiotics. 

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