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Team:Alberta-North-RBI E/Project
From 2012e.igem.org
Upcycled Aromatics - The Idea
Executive Summary
New developments in synthetic biology have allowed scientists to explore innovative ways of producing important, high-value chemicals from what was once seen as industrial waste. Paper mills and recycling plants, as a byproduct of their operation, produce a waste sludge composed of paper fibres too short for further processing. As this waste is seen as having negative value (requiring money to be disposed of), this is an attractive source of potentially exploitable cellulose. On the other end, aromatics represent a potentially lucrative chemical endpoint, having high price per unit mass and a wide variety of applications as feedstocks in a number of industries. Where others see waste, we at Upcycled Aromatics see opportunity. Our mission is to create an innovative, green, and inexpensive source of vital, high-demand aromatic chemicals by using the principles of synthetic biology.
Our proposed process has two parts: in the first, cellulose from waste sludge from recycling plants is converted into glucose; in the second, glucose from the first part is used as a feedstock for the biosynthesis of aromatic chemicals from genetically engineered bacteria.
In the glucose-aromatic conversion, we plan to use a single metabolic pathway in the biosynthesis of our product, with “on and off switches” at each “step”. This gives us the freedom to produce any intermediary compounds in addition to the natural end product. The current proposed pathway will allow us to produce either shikimate or cinnamic acid derivatives using the method described above, and should the market favour it, give us the flexibility to produce any other substance along the pathway.
Both shikimic acid and cinnamic acid (and its derivatives) are high-value, high-demand chemicals with steady markets and high potential for growth. Current commercial production of shikimic acid by extraction from Chinese star anise is effectively monopolized, and as seen from recent shortages in 2005, highly susceptible to the effects of a bad harvest. Meanwhile, cinnamic acid, an important precursor in the production of sweeteners and many pharmaceuticals, is produced mainly from synthesis of potentially harmful and polluting organic solvents. Upcycled Aromatics, with its innovative syn-bio approach, can provide a reliable and green source of both these vital compounds, produced from a feedstock for which there is minimal competition.
Once our project has been given the go-ahead for commercial scale-up, we plan to install our first plant directly downstream of either a paper mill or recycling facility. This will minimize transportation costs of the sludge, allowing us to spend money saved on enzymes needed for the cellulose-glucose conversion. Eventually, we hope to move towards a model with centralized production and an extensive distribution network to move goods to and from our suppliers and our plants.
The management of the company will consist of the current members of the University of Alberta iGEM Entrepreneurial team. With our extensive backgrounds in biochemistry, chemical engineering and genetics, we as a team have the knowledge and the skillset to make Upcycled Aromatics a success. Furthermore, we have also assembled a board of advisors that will provide us with the scientific and business expertise as we move forward. They include Dr. Chris Dambrowitz, who has had managerial experience with MDS Sciex (now AB Sciex), Blue Heron Biotechnology (Bothell WA), Visible Genetics (Toronto ON) and Atomic Energy of Canada Ltd (Chalk River ON), Dr. Dominic Sauvageau, who is doing research in bioprocessing strategies in microbes and has been involved with the start-up company Laborium Biopharma, Dr. Anthony Briggs of the University of Alberta Faculty of Business, who holds a M. S. from MIT Sloan and is an expert in the intellectual property of biotechnology, and Glen Penny, who is involved with a venture capital firm currently operating in the USA.
Case Study: Generic Oseltamivir
Oseltamivir, an anti-viral drug better known under the brand-name Tamiflu, was invented by Gilead Sciences and subsequently licensed to F. Hoffman La Roche Ltd. Since the 1999 launch of Tamiflu sales, over 33 million patients have been treated world-wide. A significant number of additional sales are due to stockpiling by governments around the world in preparation for an influenza pandemic. It is estimated that in 2006 Roche's production capacity will have reached 300 million doses per year. Oseltamivir is a compound for which there will continue to be a high demand. Shikimic acid, the starting material used to produce oseltamivir, is traditionally sourced from pods of the star anise plant, which grow only in the mountainous regions of China's southern provinces. Third-party suppliers, who work in close collaboration with Roche, are responsible for harvest and purification. Shikimic acid can also be produced by fermentation – a patented process licensed by Roche through which they eventually intend to produce a majority of their shikimic acid. As a result of Roche's two sourcing strategies, shikimic acid is not readily available to other drug manufacturers.
US and Canadian (?) patent protection for oseltamivir expires in 2016. It is generally accepted that in Canada generic drugs will very quickly capture approximately 80% of the market due to the “forced subsitution” required by drug insurance plans. However, generic manufacturers will be unable to produce a generic equivalent to Tamiflu if they cannot obtain shikimic acid. As a licensee of the same fermentation technology used by Roche to produce shikimic acid, Upcycled Aromatics would be ideally positioned as an alternate supplier of high quality shikimic acid. Agreements established with generic drug manufactures would allow us to capture a share of the lucrative shikimic acid market while reducing or eliminating the associated uncertainty.
Draft slide deck
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