Studies on the biosynthesis of neomycins

Abstract

This Thesis is concerned with aminoglycoside antibiotics. Novel antibiotics have been produced using idiotrophs of antibiotic-producing organisms and the biosynthesis of the neomycins has been studied using both wild-type and idiotrophs of antibiotics-producing organisms.

By incubating 2-deoxystreptamine-idiotrophs of Streptomyces with the 2-deoxystreptamine analogues 2,4-dideoxystreptamine and 2,4,5-trideoxystreptamine active aminoglycoside antibiotics, lacking the free hydroxyl groups on the aminocyclitol moiety, have been synthesized. It was demonstrated that the compounds produced have antibacterial spectra similar to the parent antibiotics but are less potent.

4-0-β-ribosyl-2,6-dideoxystreptamine was also converted into antibiotic by 2-deoxystreptamine idiotrophs of Streptomyces. The antibiotic synthesized by the 2-deoxystreptamine-idiotroph of a neomycin-producing organism was shown to be identical to deoxyneomycin. It was concluded that 4-O-β-ribosyl-2,6-dideoxystreptamine was converted into antibiotic following hydrolysis to produce 2,4-dideoxystreptamine.

When a 2-deoxystreptamine-idiotroph of the paromomycin-producing organism was incubated with neamine, neomycin was produced.

Results from experiments involving the conversion of ( ³H:¹⁴C) neamine into neomycin showed that neamine was converted into antibiotic intact and without prior hydrolysis.

From this latter observation a pathway for neomycin biosynthesis, involving the intermediacy of neamine is proposed.

More information

Identifiers

Catalogue record

Export record