Learn from Microbial Intelligence for Avermectin Overproduction

One of the major limiting factors in Natural products drug discovery is that pharmaceutical companies have been traditionally designed to target individual factors in a disease system, but diseases are complex in nature and vulnerable at multiple attacks. Therefore, a systematic novel synergistic drug screening approach based on a multifactorial principle is urgently needed, especially from microbial natural product library1-2. Avermectin is identified as a potent antibiotic agent for drug-resistant pathogens by a high-throughput synergy screening strategy3-7. The production of drugable secondary metabolites from microbial producers could be further increased by synthetic biology approaches. We focused on the design and synthesis of biological chassis, parts, device and modules from the microbial diversity to reconstruct and optimize their dynamical process, as well as predict favorable effective overproduction of Avermectin B1a by a 5M strategy8-9. Avermectins are exclusively made in China now and lessons learned from the success of avermectins may help transform Actinomycetes into a true power- house of innovation.