Understanding enzymes that make antibiotic for drug-resistant pathogen

One of the WHO's three critical priority pathogens, Acinetobacter baumannii, for which new antibiotics are urgently needed is one step closer to being tackled, as researchers from the Department of Chemistry -- University of Warwick have made a breakthrough in understanding the enzymes that assemble the antibiotic enacyloxin.

Acinetobacter baumannii is a pathogen that causes hospital-acquired infections that are very difficult to treat, because they are resistant to most currently available antibiotics.

In a previous paper, researchers at the University of Warwick and Cardiff University showed that a molecule called enacyloxin is effective against Acinetobacter baumannii. However, the molecule needs to be engineered to make it suitable for treating infections caused by the pathogen in humans.

The first step to achieving this is to understand the molecular mechanisms used to assemble enacyloxin by the bacterium that makes it. In their paper 'A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis' published in the journal Nature Chemistry, the researchers identify the enzymes responsible for joining the two components of the antibiotic together.

The key enzyme in this process was found to be promiscuous, suggesting it could be harnessed to produce structurally modified versions of the antibiotic.

See:

Simone Kosol, Angelo Gallo, Daniel Griffiths, et al. Structural basis for chain release from the enacyloxin polyketide synthase. Nature Chemistry, 2019; DOI: 10.1038/s41557-019-0335-5

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology