Biosynthesis of Aminoglycoside Antibiotics
Summary
Aminoglycoside antibiotics constitute a class of potent bactericidal agents characterised by aminosugar moieties linked to an aminocyclitol core. Produced predominantly by actinomycetes, these compounds are assembled via modular biosynthetic gene clusters that encode enzymes for sugar activation, glycosyl transfer, oxidation, methylation and deoxygenation. The pathway typically commences with the formation of 2-deoxystreptamine, an aminocyclitol scaffold that is successively decorated with one or more aminosugars through glycosyltransferases. Subsequent tailoring by radical S-adenosylmethionine (SAM) enzymes, pyridoxal-5′-phosphate (PLP)-dependent transaminases and various methyltransferases yields structural diversity and defines clinical properties. Combinatorial biosynthesis and pathway engineering have opened avenues to novel analogues with improved potency or reduced toxicity. Understanding the interplay among pathway-specific regulators, cofactor supply and cellular metabolism is critical for optimising fermentation titres and for the rational design of new derivatives. This foundational knowledge underpins efforts to combat emerging resistance by generating next-generation aminoglycosides and broadens our grasp of enzymatic versatility in complex natural-product assembly.
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Biosynthesis of Aminoglycoside Antibiotics publication trend
The graph below shows the total number of articles in biosynthesis of aminoglycoside antibiotics across all publications each year (not limited to Nature Index journals).
Technical terms
Aminoglycoside antibiotic: A class of natural or semisynthetic compounds featuring aminosugar residues attached to an aminocyclitol core, effective against Gram-negative bacteria.
Biosynthetic gene cluster (BGC): A contiguous set of genes encoding enzymes and regulators required for the assembly and modification of a natural product.
Pyridoxal-5′-phosphate (PLP): A cofactor derived from vitamin B₆ that facilitates transamination, decarboxylation and other amino-group transformations.
Radical SAM enzyme: A family of iron–sulphur proteins that generate radical intermediates from S-adenosylmethionine to catalyse challenging chemical transformations.
Epimerisation: The stereochemical inversion at a single stereocentre, often catalysed by specialised isomerases in sugar-modifying pathways.
References
- Recent advances in the biosynthesis and production optimization of gentamicin: A critical review. Synthetic and Systems Biotechnology (2024).
- Improving the production of carbamoyltobramycin by an industrial Streptoalloteichus tenebrarius through metabolic engineering. Applied Microbiology and Biotechnology (2024).
- Structural and Functional Basis of GenB2 Isomerase Activity from Gentamicin Biosynthesis. ACS Chemical Biology (2024).
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