There are many aminoglycosides in medical use and are all derived from actinomyces spp.

For example; streptomycin (S. griseus), gentamicin (Micromonospora purpurea), tobramycin

(S. teriebrarius), kanamycin (S. kanamyceticus). sisomicin (M. inyoesis). Some have been
modified chemically to produce derivatives with resistance to clinical isolates with acquired
resistance to earlier aminoglycoside types. Of particular interest is the use of the hydroxy-γ-
aminobutyryl side chain to give anti-pseudomonal activity to amikacin. This side chain
occurs naturally in the aminoglycoside butirosin produced by Bacillus circulans. Netilmicin is
chemically derived from sisomisin. Bacterial resistance occurs by enzymatic modification,
e.g. acylation, phosphorylation or adenylation of the various amine and hydroxyl groups. All
ring structures of these antibiotics are derived from glucose, synthesised separately and then
assembled into the final molecule. Most of the biosynthetic enzymes and their associated
genes have been identified. Many similarities in biosynthesis have been seen across the wide
variety of aminoglycosides. In addition one culture can produce a variety of molecules e.g.
kanamycin A, B, C or gentamicin C1, C2, C1a, C2a. Recombinant DNA techniques have been
used to produce hybrid aminoglycosides (Mutasynthesis), and many novel structures have
been produced. However, none has been found to be superior to existing structures. Strain
improvement programmes have been successful in increasing fermentation titres to 15-20 mg
ml-1. Additional challenges have been to either reduce the production or unwanted products
e.g. kanamycin C, or maintain the required ratios, e.g. gentamicin C1, C2, C1a.

Large-scale fermentations of aminoglycosides have several similar features. Use of soy

products is common, e.g. soy flour or soy meal. Antibiotic synthesis is sensitive to feedback
repression by glucose, ammonia and phosphate. For these reasons ammonium and phosphate
salts are not used in the starting batch. Nitrogen is obtained from the slow metabolism of the
soy proteins and the necessary phosphate is obtained from organic sources such as physic
acid. Starch is commonly used in the starting batch as streptomyces have poor amylase
activities and the release of glucose is slow and rate limiting. Alternatively, corn syrups can
be fed at predetermined rates.