Hunting for totally new bacterial natural products

Bacterial genomes contains numerous biosynthetic gene clusters (BGCs) which have contributed more than half of the small-molecule drugs used in the clinic (antibiotics, antivirus, cancer chemotherapies, etc.). Current methods of their genome mining are based on searching for signature genes or motifs extracted from known BGCs. Although very powerful, this strategy will overlook the new BGCs that don’t have enough similarity to known ones. The aim of this project is to do BGC prediction independent of prior knowledge and to obtain totally new natural products by BGC cloning and heterologous expression. The project is based on the hypothesis that useful BGCs are frequently shared by different bacteria through horizontal gene transfer (HGT) so they can be detected by looking for the transferred gene blocks across genomes. In a proof of concept test, BGCs of known antibitoics were correctly detected by two-genome comparison. As the number of sequenced bacterial genomes is large and keeps increasing dramatically (241,993 on 15/03/2020), this project holds potential to find totally new natural products that can lead to new antibiotics, antivirus or other bioproducts.