Team:Alberta-North-RBI E/projectlandscape

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==The Competitive Landscape==
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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[cite]. 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.
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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.
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=='''Our Competition'''==
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As outlined in [https://static.igem.org/mediawiki/2012e/f/fb/Global_Specialty_Chemicals_Profile.pdf the specialty chemicals profile,] the market seems poised to grow at a reliable rate. Information pertaining to our chemicals specifically are found below.
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Current industrial production already involves fermentation of genetically modified E. coli to a limited extent, Upcycled Aromatics can offer a green and reliable souce of shikimic acid.
 
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==Shikimic Acid==
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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].
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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. The Roche group's method of extraction involves isolating the compound from Chinese star anise, at a yield of approximately [http://www.roche.com/med_mbtamiflu05e.pdf 30g of seed to every 1g of shikimate]. In addition to being ineffient, the harvest itself is labor intensive and highly polluting. Furthermore, as demonstrated by the Tamiflu® shortages announced by Roche in 2005, a bad harvest will inevitably lead to mass shortages in the drug supply. With Roche's per annum production capacity reaching [http://www.roche.com/med_mb091105jvk.pdf 300 million treatments of Tamiflu in 2007 (ten times the amount produced in mid-2003)], and taking into account the possibility of another flu pandemic scare, the shikimic acid market has the potential for explosive growth.
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Major producers include Bayer (Germany), DSM (Netherlands), and Kay Fries (USA) [ibid].
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With this in mind, academics have disputed the infeasibility of producing the chemical by other means. Alternative routes to Tamiflu® or sources of 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.
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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.
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Current industrial production already involves fermentation of genetically modified'' E. coli'', but '''Upcycled Aromatics''' can offer a green and reliable souce of shikimic acid.
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===Intellectual Property Concerns===
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Our proposed feedstock, paper and recycling mill sludge, has little to no market competition due to its widespread perception as waste with negative value. 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 undeveloped.
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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 [http://www.roche.com/med_mbtamiflu05e.pdf fermentation from ''E. coli'']. '''Upcycled Aromatics''' is currently negotiating for a license from Michigan State University valued at an approximate initial cost of $25,000 and 2% of our overall profit.
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==Cinnamic Acid==
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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 market demand. The scale of annual global production was in the thousands for the year 2000, and is growing as  [http://onlinelibrary.wiley.com/doi/10.1002/14356007.a07_099/pdf demand for artificial sweeteners increases].
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Major producers include Bayer (Germany), DSM (Netherlands), and Kay Fries (USA).
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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 [http://www.scribd.com/doc/30133427/Cinnamic-Acid-Cinnamaldehyde-And-Cinnamyl-Alcohol 80% cinnamic acid based on consumed benzaldehyde]. Although the aforementioned method is one of the oldest, most well-known, our process avoids the use of polluting organic solvents in favour of biotransformation.
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==4-Hydroxycinnamic Acid==
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4-hydroxycinnamic acid is a hydroxy derivative of cinnamic acid. It is an important component in flavors, perfumes, synthetic indigo and pharmaceuticals. 4-hydroxycinnamic acid can be found in a wide variety of edible plants including peanuts, navy beans, tomatoes, carrots and garlic. The market for 4-hydroxycinnamic acid is similar to cinnamic acid, however, its value is approximately three times that of cinnamic acid. This makes 4-hydroxycinnamic acid a highly desirable end product.
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Pharmaceuticals represent the most abundant market for 4-hydroxycinnamic acid. Pharmalogical actions include anti-infective agents, antioxidants, male contraceptive agents and free radical scavengers.
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Typically, the chemical is produces by biosynthesis from cinnamic acid by the action of the P-450-deoendent enzyme 4-cinnamic acid hydoxylase. It is also produced from L-tyrosine by the action of tyrosine ammonia lyase.
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==Feedstock==
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Our proposed feedstocks, paper mill and recycled paper sludges, have little to no market competition due to their widespread perception as waste with negative value. This actually results in a disposal cost for the recycling plants and mills. The conversion of sludge to glucose shows promise [http://www.ncsu.edu/bioresources/BioRes_06/BioRes_06_4_4739_Banerjee_Glucose_Paper_Mill_Sludge_2141.pdf]. Other possible uses include feedstock for the production of ethanol, but other possible applications remain relatively undeveloped. As such, we expect to be able to acquire large amounts of our feedstock easily and cheaply.

Latest revision as of 17:56, 27 October 2012

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Contents

Our Competition

As outlined in the specialty chemicals profile, the market seems poised to grow at a reliable rate. Information pertaining to our chemicals specifically are found below.


Shikimic Acid

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. The Roche group's method of extraction involves isolating the compound from Chinese star anise, at a yield of approximately 30g of seed to every 1g of shikimate. In addition to being ineffient, the harvest itself is labor intensive and highly polluting. Furthermore, as demonstrated by the Tamiflu® shortages announced by Roche in 2005, a bad harvest will inevitably lead to mass shortages in the drug supply. With Roche's per annum production capacity reaching 300 million treatments of Tamiflu in 2007 (ten times the amount produced in mid-2003), and taking into account the possibility of another flu pandemic scare, the shikimic acid market has the potential for explosive growth.


With this in mind, academics have disputed the infeasibility of producing the chemical by other means. Alternative routes to Tamiflu® or sources of 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 [1], as well as extraction of shikimic acid from pine needles [2]. 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, but Upcycled Aromatics can offer a green and reliable souce of shikimic acid.

Intellectual Property Concerns

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. Upcycled Aromatics is currently negotiating for a license from Michigan State University valued at an approximate initial cost of $25,000 and 2% of our overall profit.

Cinnamic Acid

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 market demand. The scale of annual global production was in the thousands for the year 2000, and is growing as demand for artificial sweeteners increases.


Major producers include Bayer (Germany), DSM (Netherlands), and Kay Fries (USA).


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. Although the aforementioned method is one of the oldest, most well-known, our process avoids the use of polluting organic solvents in favour of biotransformation.


4-Hydroxycinnamic Acid

4-hydroxycinnamic acid is a hydroxy derivative of cinnamic acid. It is an important component in flavors, perfumes, synthetic indigo and pharmaceuticals. 4-hydroxycinnamic acid can be found in a wide variety of edible plants including peanuts, navy beans, tomatoes, carrots and garlic. The market for 4-hydroxycinnamic acid is similar to cinnamic acid, however, its value is approximately three times that of cinnamic acid. This makes 4-hydroxycinnamic acid a highly desirable end product.


Pharmaceuticals represent the most abundant market for 4-hydroxycinnamic acid. Pharmalogical actions include anti-infective agents, antioxidants, male contraceptive agents and free radical scavengers.


Typically, the chemical is produces by biosynthesis from cinnamic acid by the action of the P-450-deoendent enzyme 4-cinnamic acid hydoxylase. It is also produced from L-tyrosine by the action of tyrosine ammonia lyase.



Feedstock

Our proposed feedstocks, paper mill and recycled paper sludges, have little to no market competition due to their widespread perception as waste with negative value. This actually results in a disposal cost for the recycling plants and mills. The conversion of sludge to glucose shows promise [3]. Other possible uses include feedstock for the production of ethanol, but other possible applications remain relatively undeveloped. As such, we expect to be able to acquire large amounts of our feedstock easily and cheaply.




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