Aminoglycosides, genes and regulation.

A major role has been played by aminoglycoside research in the development of fermentation science especially involving genetics and regulation. The first report of the use of an antibiotic to select high producers of that antibiotic was done with the streptomycin producer. Mutational biosynthesis of new antibiotics originated with studies on the neomycin producer. The first demonstration of the presence of genes coding for antibiotic inactivation in antibiotic producers was made with Streptomyces griseus, the producer of streptomycin. Induction of an enzyme involved in secondary metabolism was found first with mannosidostreptomycinase. The first example of a nonprecursor molecule which could induce an entire antibiotic biosynthetic pathway was A-Factor involved in streptomycin production. Glucose repression and amino acid repression of mannosidostreptomycinase were the first examples of carbon catabolite repression and nitrogen metabolite repression respectively of an enzyme involved in secondary metabolism. Data supporting the occurrence of nitrogen metabolite regulation of antibiotic biosynthesis were first gathered in the early days of development of the streptomycin fermentation when it was found that the slowly used soybean meal and proline were the best nitrogen sources for antibiotic production. Aminoglycoside research also provided the first explanation of a mechanism of phosphate control of antibiotic biosynthesis. The first indication that antibiotic formation is not obligatory for spore formation was provided by data on streptomycin production.