The Renaissance of Microbial Cultivation in Support of Biodiscovery

Microbes, including bacteria, present a rich source of natural products and catalysts for health and biotech applications. While many microbes can be cultured, we are unable to cultivate the vast majority of microbes and large amounts of NPCs remain undiscovered! I am proposing a radically new approach to bring hitherto non-cultivable bacteria in cultivation. My approach is based on the fact that microbes typically grow in nutrient-poor environments, which contrasts with laboratory conditions needed to get high-density cultures. Under nutrient-rich conditions, toxic side-product of microbial metabolism can be generated. While most microbes in culture can defend against such side products, most microbes in the environment cannot. Hence, I will develop the tools and methods to augment microbes with the genes necessary to become resistant to such toxic byproducts. This radically new augmentation approach is based on constructing gene-expression cassettes on mobile genetic elements that can spread to a wide diversity of bacteria.  I will optimize the delivery of these genetic elements to environmental bacteria. I will demonstrate that these augmented cells are more diverse and have a higher degree of culturability than so far observed. As proof of principle, these cells will be screened for novel NPCs. This radical new way to enhance culturability will provide access to an enormously expanded range of NPCs for health and biotech applications.