A Probiotic Cell Factory for Production & Delivery of Supplements

Growing restrictions on antibiotics and other growth promoters in the livestock industry has left anacute need for alternative supplements to enhance animal growth and prevent infection. NorthStarMicrobes aims to address these issues by using synthetic biology to develop a probiotic cell factoryto produce and deliver performance supplements to livestock. Engineered probiotics represent aninnovative approach with several advantages to traditional chemical or fermentative synthesismethods. By employing a probiotic cell factory the supplement is produced in situ eliminatingproduct loss during purification and processing and overcoming the biggest problem associatedwith fermentation processes - inability to reach economically viable titer and rate. Furthermore insitu production allows for delivery of less stable supplements not suitable for traditional oraldelivery. The objective of this proposal is combine state-of-the-art developments in syntheticbiology to develop E. coli Nissle (EcN) a probiotic with proven gut health benefits as a chassis todeliver high-performance supplements directly in the gut. These improvements include (i)developing a suite of promoter systems that provide desired expression in the intestinal tract (ii)incorporating a basic metabolic structure that is conducive to high level product formation and (iii)incorporating a self-destruction switch triggered outside the GI tract as a biocontainment measure.Each of these improvements are structured as independent objectives to allow advancing the toolsin parallel. Successful completion will provide a chassis for the production of a supplements acrossa variety of species. This project is directly in line with USDA SBIR priorities to develop newtechnologies to increase the competitiveness of agriculturally derived products.