Team:Alberta-North-RBI E/projectlandscape
From 2012e.igem.org
The Competitive Landscape
Shikimic acid is a vital precursor to and major bottleneck in the production of the anti-influenza drug Tamiflu. Taking into account the recent H1N1 and H5N1 influenza outbreaks and reports of shikimic acid shortages in 2005, demand for the chemical seems likely to increase should another pandemic scare occur. Currently, pharmaceuticals giant Roche produces the majority of the world's supply of shikimic acid, holding an effective monopoly on the market. Their method of extraction involves isolating the compound from Chinese star anise, at a yield of approximately 30g of seed to very 1g of shikimate[http://www.roche.com/med_mb091105jvk.pdf]. Furthermore, as demonstrated by the Tamiflu shortages announced by Roche in 2005, a bad harvest will lead inevitably lead to mass shortages in the drug supply.
With this in mind, academics have disputed the infeasibility of producing the chemical by other means. Alternative routes to Tamiflu or sources shikimic acid may prove to be possible sources of competition for Upcycled Aromatics' major market. They include the usage of aminoshikimic acid, biosynthesized by genetically modified baceria, over shikimic acid as a chemical starting point [http://pubs.acs.org/doi/abs/10.1021/ol049666e], as well as extraction of shikimic acid from pine needles [http://www.ncbi.nlm.nih.gov/pubmed/21243780]. However, commercial viability on scale-up has yet to be proven for most proposed processes.
Current industrial production already involves fermentation of genetically modified E. coli to a limited extent, but Upcycled Aromatics can offer a green and reliable souce of shikimic acid.
Intellectual property rights to the current proposed biosynthetic process to be used in our organism are held by the researchers from the Frost group at Michigan State University. Roche currently holds a non-exclusive license for this technology and reports that in 2006, the majority of shikimic acid production was produced by fermentation from E. coli[http://www.roche.com/med_mbtamiflu05e.pdf]. Upcycled Aromatics has obtained a license for this technology valued at a flat value of $25,000 and 2% of overall profit.
Cinnamic acid, converted to its ester form, is an organic chemical with a wide variety of applications ranging from sweeteners to pharmaceuticals. Although its value may be lower on a per gram basis when compared to shikimic acid, a wider variety of applications may mean increased profits depending on current demand. The scale of annual global production is in the thousands on tons as of the year 2000, and is likely to grow as demand for artificial sweeteners increases [http://onlinelibrary.wiley.com/doi/10.1002/14356007.a07_099/pdf].
Major producers include Bayer (Germany), DSM (Netherlands), and Kay Fries (USA) [ibid].
Typically, the chemical is produced by a condensation of benzaldehyde and acetic anhydride in the presence of a sodium acetate catalyst, and can yield over 80% cinnamic acid based on consumed benzaldehyde [http://www.scribd.com/doc/30133427/Cinnamic-Acid-Cinnamaldehyde-And-Cinnamyl-Alcohol]. Our process avoids the use of potentially polluting organic solvents in favour of converting something with negative value (paper sludge) into a desirable high-value platform chemical.
Our proposed feedstock, paper and recycling mill sludge, has little to no market competition due to its widespread perception as a waste with negative value incurred as a result of its disposal cost. The conversion of sludge to glucose shows promise (Banerjee 2011). Other possible uses include feedstock for the production of ethanol (Furstein and Sacakerelles, 2003; Yamshita et al. 2006; Vamvuka et al. 2009; Kang et al. 2010, 2011) and lactic acid (Marques et al. 2008; Mukhopadhyay 2009), but other possible applications remain relatively undeveloped.