Biosynthetic pathways of aminoglycosides and their engineering

•Aminoglycosides have been and will be treasured anti-infective against 'superbugs'.•Aminoglycosides' defensive structural features are clues for antibiotic discovery.•Understanding aminoglycoside biosynthesis is a key for its pathway engineering.•Engineered biosynthesis will be an efficient tool to generate new aminoglycosides.

Despite decades long clinical usage, aminoglycosides still remain a valuable pharmaceutical source for fighting Gram-negative bacterial pathogens, and their newly identified bioactivities are also renewing interest in this old class of antibiotics. As Nature's gift, some aminoglycosides possess natural defensive structural elements that can circumvent drug resistance mechanisms. Thus, a detailed understanding of aminoglycoside biosynthesis will enable us to apply Nature's biosynthetic strategy towards expanding structural diversity in order to produce novel and more robust aminoglycoside analogs. The engineered biosynthesis of novel aminoglycosides is required not only to develop effective therapeutics against the emerging 'superbugs' but also to reinvigorate antibiotic lead discovery in readiness for the emerging post-antibiotic era.

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