Pharmaceutical substances of microbial origin

Microorganisms produce a wide variety of secondary metabolites, many of which display actual or potential therapeutic application. Antibiotics are by far the most numerous such substances 

Antibiotics are generally defined as low molecular mass microbial secondary metabolites which, at low concentrations, inhibit the growth of other microorganisms. To date, well in excess of 10 000 antibiotic substances have been isolated and characterized. Overall, antibiotics are a chemically heterogeneous group of molecules, although (as described later) many can be classified into different families based upon similarity of chemical structure. 

Sir Alexander Fleming first noted the ability of the mould P. notatum to produce an antibiotic substance (which he called penicillin) in 1928. However, he also noted that when penicillin was added to blood in vitro, it lost most of its antibiotic action, and Fleming consequently lost interest in his discovery. In the late 1930s, Howard Florey, Ernst Chain and Norman Heatley began to work on penicillin. They purified it and, unlike Fleming, studied its effect on live animals. They found that administration of penicillin to mice after their injection with lethal doses of streptococci protected the mice from an otherwise certain death. 

The aminoglycosides are a closely related family of antibiotics produced almost exclusively by members of the genus Streptomyces and Micromonospora (Table 1.19). Most are polycationic compounds, composed of a cyclic amino alcohol to which amino sugars are attached. They all induce their bacteriocidal effect by inhibiting protein synthesis (apparently by binding to the 30 S and, to some extent, the 50 S, ribosomal subunits). Most are orally inactive, generally necessitating their parenteral administration. 

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