Current Uses of Synthetic Biology
Conventional plastics materials like polyvinyl chloride (PVC), polyethylene teraphthalate (PET), and polypropylene (PP) are made from petroleum or fossil carbon. The PHA in Mirel bioplastics is made through the fermentation of sugar and can be biodegraded by the microbes present in natural soil or water environments. Although PHAs are produced naturally in many microorganisms, the cost and range of compositions required for successful commercialization dictated that PHA pathways had to be assembled in a robust industrial organism that does not naturally produce the product.
Metabolic pathway engineering was used to accomplish this task, relying on modern tools of biotechnology. These include DNA sequencing and synthetic construction of genes encoding the same amino acid sequence as in the donor strain, but optimized for expression in the engineered industrial host. These technologies provided rapid development and optimization of robust industrial production strains that would not have been feasible using classical techniques relying on isolation and transfer of DNA from one species to the other.
This has allowed Metabolix to successfully commercialize Mirel bioplastics. More than 50 years after it was first considered as a potentially useful new material and following several efforts by leading chemical companies to commercialize PHAs based on natural production hosts, Metabolix has made these products available at a commercial scale.
Increasing Efficiency in Bioprocessing of Pharmaceuticals
Sitagliptin, Merck’s first-in-class dipeptidyl peptidase-4 inhibitor, is marketed under the trade name Januvia® as a treatment for type II diabetes. The chemical manufacturing route to Sitagliptin developed by Merck won a Presidential Green Chemistry Challenge Award in 2006, but there were still several opportunities for improvement. Codexis and Merck collaborated to develop a novel, environmentally benign alternative manufacturing route. Using synthetic biology and its directed evolution technologies, Codexis discovered and developed a transaminase capable of enabling the new biocatalytic route, which is currently in scale-up towards commercial manufacture.
One common definition of “synthetic biology” is “the design and construction of new biological entities that do not exist in the natural world.” In this instance, there was no known enzyme that could perform the reaction required to enable the biocatalytic route. By designing and generating new enzyme variants, Codexis was able to identify a novel enzyme that provided detectable initial activity. This enzyme was then improved greater than 25,000-fold in order to generate the highly active, stable, enantioselective and practical enzyme from a starting activity that did not previously exist in the natural world. This work was awarded with the Presidential Green Chemistry Challenge Award in June, 2010.
Producing a Building Block for Everyday Products
Succinic acid is a linear 4-carbon saturated dicarboxylic acid. Myriant’s bio-succinic acid produced from renewable and sustainable raw materials is chemically identical to succinic acid produced by petrochemical routes, with a purity level equal or superior to the highest quality petroleum-based succinic acid. This enables Myriant’s bio-succinic acid to be dropped in to any process currently using petroleum derived succinic acid. In addition, its chemical structure allows it to replace several other building block chemicals currently produced from petrochemical feedstocks – including maleic anhydride and adipic acid, which are used in the production of everyday consumer items from plastics to clothing fibers and biodegradable solvents, to food and pharmaceutical products. The market potential of succinic acid is estimated to be $7.6 billion per year.
In the conventional petrochemical process, benzene or butane is oxidized to produce maleic anhydride – releasing roughly half of the raw material as CO2 – which is then converted to succinic acid through hydrolysis.
Myriant has developed a more eco-friendly method for the production of bio-succinic acid that addresses the supply, cost and environmental issues associated with the use of fossil fuels as feedstocks. Myriant’s technology platform uses proprietary microorganisms in a fermentation process designed to produce high-value bio-based chemicals with high yields and productivity. The biocatalysts are non-genetically modified (non-GMO) microorganisms with altered metabolic pathways that grow and simultaneously produce target bio-based chemicals from a variety of renewable feedstocks. Our highly efficient biocatalysts are able to flourish in minimal growth medium without the use of expensive, complex nutrients, enabling us to bring renewable chemicals to market that are cost-competitive with their petroleum based counterparts.
Myriant’s biocatalysts are able to consume a variety of readily available low-cost sugars from non-food sources, such as glucose from sorghum and cellulosic sugars from waste biomass. These raw materials are not subject to the extreme price volatility or supply availability issues associated with petroleum-based feedstocks. Additionally, Myriant’s anaerobic process consumes CO2, resulting in a reduced carbon footprint.
