Sugar-coated antibiotics

Researchers from the John Innes Centre and the University of East Anglia have recently elucidated the structure and function of an enzyme which is involved in decorating antibiotics with sugar molecules. 

Many antibiotics have a variety of different carbohydrate molecules attached to them which can help the antibiotic to be taken up by the target organism or overcome resistance.  By manipulating the sugar, it may be possible to restore usefulness in antibiotics to which resistance has developed.  
The aim of this research was to find out how these sugars are made, and how their structures affect their biological activity.

The researchers studied an enzyme from a little studied species of Streptomyces bacteria, which produces the antibiotic tylosin.

The enzyme they looked at is involved in making a sugar molecule that decorates tylosin. By working out how the carbohydrates are made, it may be possible to make unnatural sugars, with different properties.  
“This is a bit of biochemistry we can’t do with chemistry. We need to go back to the fundamentals of how these sugars are put together in nature”, said Professor Rob Field.  “We want to see what happens when we decorate an antibiotic with sugar and which sugars make the best decoration.” 
They are not yet near to a market product, but trying to understand at a fundamental level how these sugars are made.  “We are still putting the toolkit together” said Professor Field.  By modelling the enzyme, and comparing it with related enzymes, they have been able to identify the key parts needed for its function, and propose the biochemical basis for how it creates the carbohydrate’s precise structure. 
The work was co-published with Biotica, a natural products drug discovery company based in Cambridge, and was featured on the front cover of the journal ChemBioChem, and funded by the BBSRC and EPSRC. 

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