S52: Biosynthetic routes to 4,5 and 4,6-disubstituted aminoglycoside antibiotics

Abstract: Aminoglycoside antibiotics are among the oldest, and the most clinically important aminosugars primarily isolated from the various Streptomyces and Micromonospora. This study is mainly focused on the establishment of heterlogous expression of the biosynthetic gene cluster for the identification of aminoglycoside genes and expression of the recombinant minimal sets of candidate genes to prove the biosynthetic pathway of kanamycin. We were also able to modulate the kanamycin biosynthetic flux for the increased production of a valuable minor component, kanamycin B, by swapping glycosyltransferases.Co-expression of various heterologous aminoglycoside genes with selected sets of kanamycin biosynthetic genes led to the in vivo biosynthesis of (AHBA)-conjugated kanamycins. The recombinant plasmids containing genes from the spectinomycin and kanamycin biosynthetic gene clusters, were constructed to yield the novel kanamycin analog, oxykanamycin C. This is the production of novel aminoglycoside analogs.

Acknowledgments

This work was supported by the 21C Frontier Microbial Genomics and Application Center Program, Ministry of Science & Technology (Grant MG02-0301-004-2-3-1), Republic of Korea.