Disease relevance of Deoxystreptamine

• Production of antibiotics by biotransformation of 2,4,6/3,5-pentahydroxycyclohexanone and 2,4/3,5-tetrahydroxycyclohexanone by a deoxystreptamine-negative mutant of Micromonospora purpurea [1].
• By using wild-type and deoxystreptamine-negative mutants of Streptomyces fradiae grown in media containing [6(-3)H]glucose or [U-14C]glucose, and by subsequent hydrolysis of the labelled neomycin produced, neamines labelled with 3H in both rings I and II, but with 14C in ring I only, were prepared [2].
• Aminoglycoside nucleotidyltransferase 2''-I (formerly gentamicin adenylyltransferase) conveys antibiotic resistance to Gram-negative bacteria by transfer of AMP to the 2''-hydroxyl group of 4,6-substituted deoxystreptamine-containing aminoglycosides [3].
• Biosynthetic investigations of formation of DOS in actinomycetes are limited to the characterization of 2-deoxy-scyllo-inosose synthase, the first step enzyme of the DOS biosynthetic pathway [4].

High impact information on Deoxystreptamine

• Analysis of structure-activity relationships with a variety of aminoglycosides has revealed that the deoxystreptamine aminocyclitol ring plays a critical role in substrate binding [5].
• Amikacin is a derivative of kanamycin A, obtained through acetylation with the L(-)-gamma-amino-alpha-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety [6].
• The sisomicin-gentamicin resistance methylase gene (sgm) from Micromonospora zionensis (the producer of antibiotic G-52 [6-N-methyl-sisomicin]) encodes an enzyme that modifies 16S rRNA and thereby confers resistance to 4,6-disubstituted deoxystreptamine aminoglycosides [7].
• Have deoxystreptamine aminoglycoside antibiotics the same binding site on bacterial ribosomes [8]?
• These structures explain the specificity for 4,5-disubstituted 2-deoxystreptamine (DOS) derivatives and for subtype A and subtype F kissing-loop complexes, and provide a strong basis for rational drug design [9].

References