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반연희,윤여준 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0
Gentamicin, an aminoglycoside antibiotic produced by Micromonospora echinospora, is widely used to treat bacterial infections. Despite its biological significance, the exact biosynthetic route has remained unclear. We have elucidated the three hidden biosynthetic pathways leading to gentamicin B through in vitro reconstitution and discovered seven unknown minor intermediates. In addition, the crystal structure of the key enzyme detailed the low production of gentamicin B caused by narrow substrate specificity in the wild-type producer. The new gentamicin analogs showed that PTC readthrough activity similar to the natural aminoglycoside G418 was maintained, but the in vitro nephrotoxicity was reduced. This detailed understanding of gentamicin biosynthesis will be enable to use for expanding aminoglycoside structural diversity.