Difference between revisions of "Team:UCL/Xylitol"

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<h4> D-Xylitol is a sugar polyol that has been used in the food industry as a low-caloric sweetener. Also, it has reported having multiple beneficial health effects such as the prevention of dental caries, osteoporosis, and acute otitis media. Currently, D-Xylitol is commonly produced by the chemical reduction of D-Xylose presented in Xylans. However, this process represents substantial costs for the industry. We have designed a genetic circuit for the expression of the necessary enzymes for the biological production of xylitol from lignocellulose hydrolysates. </h4>
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<h4> Xylitol is a sugar polyol that has been used in the food industry as a low-caloric sweetener. It has been reported to have multiple beneficial health effects such as the prevention of dental caries, osteoporosis, and acute otitis media. Currently, xylitol is commonly produced by the chemical reduction of xylose presented in xylans. However, this process represents substantial costs for the industry. We have designed a genetic circuit for the expression of the necessary enzymes for the biological production of xylitol from lignocellulose hydrolysates for expression in E. coli for fermentation and subsequent processing.  </h4>
 
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Revision as of 22:02, 19 October 2016

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UCL iGEM 2016 | BioSynthAge

XYLITOL





1. Executive Summary


Xylitol is a sugar polyol that has been used in the food industry as a low-caloric sweetener. It has been reported to have multiple beneficial health effects such as the prevention of dental caries, osteoporosis, and acute otitis media. Currently, xylitol is commonly produced by the chemical reduction of xylose presented in xylans. However, this process represents substantial costs for the industry. We have designed a genetic circuit for the expression of the necessary enzymes for the biological production of xylitol from lignocellulose hydrolysates for expression in E. coli for fermentation and subsequent processing.


We have also created a comprehensive first iteration of a business plan for the production of Xweet, a key ingredient in tooth-decay defying sweets. We have filed a provisional patent and trademarked our more environmentally friendly method for the production of Xweet. Adopting a lean method, we have engaged extensively with the confectionary industry, prototyping Xweet confectionery and setting out a pathway for commercial success.


2. The problem explored


Through our engagement with our local elderly community we identified a demand for tea-time treats that did not cause tooth-decay or imbalances in sugar levels. Adopting a lean method, we have engaged extensively with the confectionary industry to explore London’s sugar-substituted sweet landscape to confirm this as a wider demand. Our extensive literature search drew our attention to xylitol, a sugar substitute with widely-reported health benefits but an environmentally unfavorable and expensive production process. Xylitol is a key ingredient in tooth-decay defying sweets. Speaking to the UK’s confectionary manufacturers, we confirmed demand for xylitol produced in a less expensive and more environmentally friendly way.


Demand for tooth-decay defying treats from end users


London’s ageing population have a sweet tooth. Reports show that this is due to the impact that ageing has on our taste buds. Over time our taste buds decrease in number and become less sensitive. This is compounded by the effect of age-related diseases such as Alzheimer’s and Parkinson’s Disease, with the loss of taste and smell actually becoming increasingly important in the diagnosis of these disease. This drives the increasingly sweet tooth of the ageing population which in turn drives a negative impact on the oral health of this population. The oral disease burden, of which a big part is attributable our ageing population, is causing the total oral health expenditure within the EU to rise to an enormous €93 billion in 2020. There is therefore a push in public health policy towards preventative solutions that minimize bad oral health manifested in large parts as dental caries. This demand for tooth-decay defying sweets was therefore flagged up to us through our engagement with the elderly community. They described their need for sweet treats and oral health as a constant pain throughout their ageing process.

Insert Images of Old people and us talking to them

Demand for tooth-decay defying treats from confectionary retailers

We confirmed this demand for tooth-decay defying treats through interviews with London’s sweet landscape. We identified that these outlets were experiencing a shift in their customer demands such that there is an increasingly underserved proportion of health-conscious sweet lovers. Some of the sweet shops that we interviewed made their own sweets, while most bought their sweets from confectionary manufacturers. While the total EU and US confectionary market it worth €66.75 billion, the healthy confectionary market has been increasing its share of this overall market in recent years, putting the latest market share estimate within the UK at 11%. The growth of the healthy confectionary market is 16% higher than the total average growth of the entire confectionary market. These confectionary outlets provided us with a list of sugar-substitutes that customers ask for and that are used in the production of these sweets. We partnered with staff to identify xylitol through this market research and an extensive literature search as a candidate for meeting this demand. D-Xylitol is a sugar polyol that has been used in the food industry as a low-caloric sweetener. It also has been reported as having multiple beneficial health effects such as the prevention of dental caries, osteoporosis, and acute otitis media.

Insert images of us visiting sweet shops

Demand for tooth-decay defying ingredients from confectionary manufacturing industry


Our literature research highlighted the potential of xylitol for use in tooth-decay defying sweets. It’s health benefits and positive impact on dental caries have been widely reported. We explored how xylitol is used in confectionary manufacturing to understand how more confectionary manufacturers can be enabled to use xylitol in their production processes. By visiting a chocolate manufacturing company, discussing their production process with the Operation Manager and observing their production process, we were able understand the decision making process in raw material procurement and the parameters for consideration of the material in the process. Most notably, we discovered that manufacturers prefer to use xylitol over other sugar substitutes such as coconut sugar as xylitol’s high melting temperatures makes it a manufacturer’s dream when making chocolate treats as machinery is not clogged up with caramel. However, the manufacturers hold back from using xylitol because of its associated costs and environmental impact.

Insert images of us visiting chocolate factory

2. Our Solution

We have therefore identified trapped value where in the value chain from feedstock to production of tooth-decay defying treats. We are best placed to solve this problem and have devised a plan for the production of xylitol, using synthetic biology and biochemical engineering processes, that reduces the impact on the environment and decreases associated costs. Our solution aims to supply a big proportion of the global market demand for more than 125,000 tonnes of xylitol per annum.

Insert image from https://drive.google.com/file/d/0B7It31qcREQjdkhyODRLZi1SRzg/view?usp=sharing

Our solution for the production of xylitol for supply to confectionery manufacturer involves a synthetic gene circuit in E. coli for extracellular secretion of xylitol following processing of xylan from agricultural waste in the upstream process. The downstream process involves a series of biochemical extraction and purification steps, using drastically less energy than the chemical process for xylitol production. Our xylitol product, Xweet, can be used to produce tooth-decay defying confectionery treats that utilise xylitol, at a lower price and incredibly similar taste to conventionally sugared treats.

Insert image from https://drive.google.com/file/d/0B7It31qcREQjM0RLR2s1WTdZSEU/view?usp=sharing

We prototyped a potential treat that could be made with our xylitol product. We cooked up fudge using conventional brown sugar and xylitol. We asked UCL students to compare the tastes of our two batches, two identify the better tasting batch and the one that they thought contained xylitol. 100% of all participants guessed incorrectly, failing to identify the xylitol batch correctly. This lends support to the potential for xylitol to replace sugar in a vast number of confectionery products.

Insert picture of our fudge prototype.

Using our upstream technology in a novel method for the production of xylitol from agricultural waste reduces the cost of the final product and the environmental impact. This therefore means that we are able to sell xylitol to confectionary manufacturers and the pharmaceutical industry for who the value proposition of reduced cost of raw materials and the reduced carbon footprint of their final product lifecycle contributes to the increase in profit margins. By making xylitol purchasing cheaper, moreover, we are empowering confectionary manufacturers to meet the demands of an ageing population for tooth-decay defying treats. We therefore have a unique and defendable business case.

3. Intellectual Property

Because of its technological relevance and its disclosure in this event, having an intellectual property strategy was crucial for the commercial aspects of the project. This approach has been confirmed after several discussions with numerous potential investors and advisers. Two important intellectual property figures were considered for this project, a patent and a trademark.


Patent


Initially, we performed a search in the database (Espacenet) from the European Patent Office. The results were encouraging because no result was similar to our invention after using (in different combinations) the keywords: xylitol, cell, surface, display. However, considering the possibility of not complying with the novelty feature, we searched for scientific articles that could describe a similar technology. From the results, we found that Guirimand et al. published in 2015 a similar system. The researchers reported the surface display of four enzymes (Xylose reductase, ß-glucosidase, xylosidase and xylanase) on yeast for the conversion of xylans into xylitol. Despite its likeness, our proposed project differs in (1) the displayed enzymes, (2) the host organism, (3) the oscillating phenotype of the enzymatic expression. Following this, we found that our invention could fulfill the three patent features and therefore our invention was fully patentable.


This intellectual property search allowed us to define the claims for our patent application. We filed a provisional patent application with the UK Intellectual Property Office using the presented form with the application number 1616500.3. The relevant documents for this application are presented below:

1. Filed Form

2. Receipt


We are currently working on an international patent application (PCT) for our invention. This strategy grants us additional time for starting patent applications simultaneously in 140 countries.


Trademark


Continuing with our intellectual property strategy, we have been working on filing a trademark application with the UK Intellectual Property Office for the brand and the logo of our final product, Xweet. This allows us to distribute an early version of the product to different stakeholders while building a product identity.