Mining genomes to find new antibiotics

Antimicrobial resistance – resistance to antibiotics – is becoming an urgent and dangerous global problem. When a particular antibiotic is overused, bacteria eventually evolve in a way that that the antibiotic no longer works on them. This is how 'superbugs' such as MRSA have come about. And this is why new types of antibiotics are always needed.

Scientists in Germany are rising to the challenge by developing better ways of looking for natural products that could have enhanced antimicrobial properties. Professor Rolf Müller, of the Helmholtz-Institute for Pharmaceutical Research, says: "As most antibiotics originate from microorganisms that have complex gene clusters – including very large genes – we aimed to develop a strategy to better obtain and modify those genes."

The group have developed genetic tools based on a gene-synthesis platform – a method used to prepare genes of interest. They aim to identify and make use of the pathways that organisms use in nature to make complex products, using restriction nucleases – that is enzymes that cut DNA into specific fragments – to cut up and reassemble small fragments of DNA. This enables an improved design of natural product biosynthesis genes, which can be used to prepare new compounds of interest. It’s a relatively straightforward method that they believe will help other scientists to design better antibiotics in the future.

"The strategy described in this paper could help facilitate the exploitation of natural product biosynthetic pathways via genome-mining approaches", says Professor Müller. "It bears potential for the discovery of novel natural products, and relieve the situation of antimicrobial resistance."

This article is free to read in our open access, flagship journal Chemical Science: Alexandre Homberg et al., Chem. Sci., 2018, Accepted Manuscript. DOI: 10.1039/C8SC02046A. You can access all of our ChemSci Picks in this article collection.