With an antimicrobial resistance crisis looming on the public health horizon and a generation of antibiotic treatments falling victim to drug-resistant bacteria, the search for new antibiotics and antimicrobial agents is more important than ever. The natural world remains a supreme source of products that could drive the next wave of effective antibiotics, with bacterial metabolites proving to be a particularly rich wellspring of clinically promising compounds.
Genome mining techniques allow researchers to sequence bacterial genomes for in-depth study, hunting for clinically relevant gene clusters responsible for encoding the secondary metabolites that don’t influence a micro-organism’s growth, development or reproduction but often play a role in defending against bacterial predators.
This genome mining process is labour-intensive, and because of its place in the early stages of the drug discovery process, has increasingly proven too high-risk for significant investment from the biotech and pharma sectors. Bacterial genome screening, then, is primarily driven by smaller groups of academic researchers.
Nevertheless, data analytics technologies are helping to speed up the search for metabolites, none more so than antiSMASH, an open-source software suite that allows the rapid genome-wide identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genomes. It integrates and cross-links with a large number of computer-simulated secondary metabolite analysis tools that have already been published.
Initially developed by Kai Blin and Marnix Medema in 2010 when they were both PhD students in Germany and the Netherlands respectively, antiSMASH has now become ubiquitous among natural product researchers doing bacterial and fungal genome mining, with more than 418,000 jobs processed to date and contributions coming from research groups all over the world. More recently, the team behind the software launched the antiSMASH database, helping researchers to save time by allowing them to search for pre-calculated antiSMASH results from nearly 25,000 full and draft genomes.
Here, antiSMASH co-creator Kai Blin, who now works at the Technical University of Denmark’s Novo Nordisk Foundation as a researcher and scientific software engineer, elaborates on the benefits of antiSMASH and its database, and the advantages of an open-source approach to scientific software design.