Bioengineering a non-pathogenic bacteria to produce medically-relevant biopolymers

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Project Summary/Abstract Alginate is a biopolymer with a wide array of applications in, food, personal care products and biomedicine. In addition to its role as a tablet excipient and antacid treatment, alginates play an important role as a non- adherent, exudate absorbing gel, for advanced wound care dressings. Historically, alginates for this application have been obtained from brown seaweed, but the problems with this source include decreasing yield, demand that is larger than the supply, and a fixed polymer composition that cannot be changed to produce unique alginates customized to enhance wound closure and prevent infections. Certain species of bacteria (Azotobacter, Pseudomonas) produce alginate, but commercialization has been blocked by decreased or unstable synthesis of this polymer in culture. Breakthrough and patented technology was developed by Progenesis co-founder, Dr. Hongwei Yu that involves a genetic signal to activate high and stable production in an engineered strain of P. aeruginosa. The product of this SBIR project will be alginates of different monomer compositions and modification (acetylation) that are not produced by seaweed. These alginates will produce sodium or calcium gels with varying tensile strength, pore size, fluid retention and drug release rates that can be customized for improving the effectiveness of their application for alginate wound dressing. In the Phase I project, a strain of P. aeruginosa, PGN5 was engineered that lacked the genes encoding products of concern to the FDA and essential to pathogenesis. PGN5 is non-pathogenic in mice similar to the FDA-approved E coli K12. In this phase II proposal Progenesis will further bio-engineer the PGN5 strain to produce alginates that will form gels of different tensile strength, porosity and fluid adsorption capability so that alginate wound dressings can be individualized for each patient’s needs (aim1). Aim 2 will determine the physical-chemical properties necessary to reduce wound closure time by 20% relative to seaweed alginate dressings. To ensure adequate supply and profit margin Progenesis will bio-engineer central carbon metabolism to increase the current yield of alginates by 50% and scale up to a 45L bioreactor (aim 3). Achieving these aims will allow Progenesis to produce unique alginates tailored to enhance the healing of chronic wounds with a reported 2014 global market of $9.9 billion USD. Alginate containing dressings comprise about 5-7% of the market, ~$690 million USD. They are also the component of wound care that has the highest projected CAGR growth rate (16%) through 2021. The preclinical data will be used to develop R&D agreements containing milestone payments with companies selling wound care products. Also licensing agreements will be sought with companies producing seaweed alginate providing additional cash flow from royalties. Progenesis will also market its suite of alginates to R&D laboratories for use in various research applications such as stem cell differentiation, 3-D cancer cell growth, and tissue engineering. This will provide a revenue stream while R&D and licensing agreements are negotiated.