Medicines from microbes

Marnix Medema, winner NBIC Young Investigator Award 2014

That microbes are great manufacturers of all kinds of useful compounds is nothing new. But we probably can deploy the capabilities of these miniature factories much more targeted if we increase our understanding on their metabolism. Marnix Medema (Max Planck Institute for Marine Biology, Bremen) is certainly doing his bit in this respect.

IMG_2036He was honoured with the NBIC Young Investigator Award 2014 for this PhD thesis ‘Medicine from Microbes’ with which he graduated from the University of Groningen. We should focus on secondary metabolism, according to Medema. “That is a great source of valuable molecules.” He advocates a shift in focus from individual genes to gene clusters. “It is not so much about finding one gene that is associated with a certain biosynthesis, but about biosynthetic gene clusters. Those are interesting for engineering purposes.” There will be no shortage of microbial genomes to work with, says Medema. “Currently, around 40,000 microbial genome projects are ongoing and 100,000s of microbial genomes will become available in the coming years.” All this genomic data can be approached in different ways to identify relevant gene clusters. Studies showed that chemical structure elucidation can help. For example, there are indications towards a shared aryl-polyene scaffold, pointing to similar gene clusters in very distantly related microbes. High throughput characterization of metabolites is another relevant approach, such as using mass spectrometry (MS) methods to detect peptide-like compounds. Medema mentions Pep2Path as an example. “It takes in MS mass shift data and genome sequences to match amino acid search tags to mass shifts. That can point us to matching molecules to gene clusters.” He emphasizes that although biological understanding is necessary, engineering is his primary goal. “But you cannot simply couple different building blocks and expect your product to just come rolling out. After all, nature is not LEGO.”