Tech Review

Manufacturing new platform chemicals

16.06.2010

Exactly two years ago, DNP Green Technology (www.dnpgreen.com) and Agro-industries Recherches et Développements (www.a-r-d.fr) officially announced that they were forming the joint venture Bioamber S.A.S (www.bioamber.com) with the aim of commercialising technologies for producing succinic acid originating from vegetable sources. At that time, one of the venture’s major milestones was to build the first ever commercial bio-based succinic acid plant. In December of 2009, Bio­amber successfully began production at its Pomacle-Bazancourt bio­refinery located in the Champagne region of France. For its pio­neering lead in the field and its efforts to commercialise bio-based succinic acid, the consultant firm Frost & Sullivan awarded Bioamber its Technology Innovation Award in 2009.

With 2,000 metric tons of annual capacity, the new plant is the first and only bio- succinic acid production plant in the world. Following in the footsteps of other successful ventures such as DuPont Tate and Lyle’s 1,3-PDO plant, the project provides even more proof that industrial biotechnologies can substantially modify the competitive landscape in the chemical industry. Bioamber’s goal was to make succinic acid widely available and competitive with other di-

acids such as maleic anhydride or adipic acid. And after four years of development, the company is getting there.
Since 2007, Bioamber has used its 80m3 pilot plant to produce samples for its clients all over the world. Along with major applications in the production of materials based on di-acids – among them polyesters (PBS) and polyurethane – other applications include cosmetics, plasticisers or even de-­icing substances. In a close relationship with its partner Basic Solutions, Bioamber has now developed a revolutionary succinate-based de-icer with a greener and far less corrosive profile than existing formulations. In addition to this de-icer development, Bioamber has sent samples to more than fifty companies all over the world to help these customers start their own development efforts and expand the market for succinic acid. All of those customers have validated the purity of Bioamber’s succinic acid.

Metabolically engineered E. coli

Based on an engineered E. Coli licensed from the US Department of Energy, Bioamber has developed a proprietary and innovative fermentation technology that delivers cost-effective bio-succinic acid. With three gene knock-outs, the strain initially developed at the US DOE offers very attractive yield and productivity coupled with very few by-products (such as acetic acid) which are separated during the fermentation process. An equally important aspect is that the bacteria sequesters carbon dioxide during the production process. A recent carbon-14 analysis demonstrated that 72% of the carbon comes from the glucose in the process, while approximately 28% comes from CO2. That study validates the theory that one glucose and two CO2 molecules are used to make two four-carbon succinic acid molecules. This confirmation was necessary to convince Bio­amber’s licensees that our technology will generate carbon credits by fixing CO2, thereby improving the overall economics. Another benefit is the ability of the strain to grow on a variety of raw materials, including sucrose, glucose and glycerol. The E.Coli strain works well on all these carbohydrates. Consequently, Bioamber’s technology is not corn-dependent, and can be used in various geographical locations. In addition, the bacteria can easily switch from one source to another, depending on how costs evolve for the raw materials, at no additional expense. This flexibility provides a high degree of cost stability.

The goal is licensing

In the long term, Bioamber does not plan to build larger plants. Instead, our business model is to outlicense the technology to industrial partners entering this attractive market segment. The existing plant will be used to validate the technology and expand the market in order to limit the risk inherent in such an investment. Partners will want to keep their exposure to a minimum as they enter the market, and to avoid assuming both commercial and technical risks from the start. As the latter is covered by the Bioamber joint venture, licensees can concentrate their efforts on the business end. The company is currently in discussions with several multinationals in Europe, North America and Asia, and does not expect to have only one major production plant covering the entire market. Instead, the goal is to have several plants on each continent. Logistics costs are significant for a commodity chemical like succinic acid, and it is simply not cost-effective to produce in Europe and sell in Asia. At least mid-term, this problem has to be solved by having a product­ion plant on each continent, and Bioamber is getting there by negotiating licenses with several well-known firms.

Three pillar process

Along with the development work done at its production plant, Bioamber also pursues various R&D programs in order to maintain its technological leadership and constantly improve its cost structure. Our licensees want to be reassured that we maintain forefront R&D activities in order to benefit from the best-in-class IP portfolio and know-how. It is also mandatory that Bioamber build barriers-to-entry. These R&D programmes cover the strain itself, as well the fermentation and downstream processes. A fermentation process is actually a three-pillar technology based on the strain itself, the fermentation process, and the downstream process. All three are equally important, and must be constantly improved. An excellent strain is nothing without an efficient downstream. In fact, a highly innovative downstream process can significantly improve overall performance.
In terms of applications, the key word is 1,4-butanediol. There are several off-the-shelf hydrogenation technologies able to convert succinic acid into 1,4-butanediol, but few of them offer a selective and competitive route to this Holy Grail. The current market for the substance is estimated at 1.3 million tonnes per annum, and has a CAGR of 6%. Today we can offer the market an integrated technology that converts glucose into 1,4-butanediol. Some start-ups are developing technologies for in-cell production of this diol from sugar, but they will face major issues. First, the molecule dissolves the cell membrane, and is therefore toxic for the strain. Second, production yield will be much lower than that of succinic-based technologies. Finally, several distillation steps are necessary to extract the diol from the fermentation broth. We do not believe that it will be possible to develop a cost-effective in-cellular route to 1,4-butanediol. Obtaining a pure product will also consume huge amounts of energy, which means a non-green process.

Market for butanediol

The technology developments around bio-based succinic acid began at the US Department of Energy in the mid-1990s. In 2004, the widely publicised US DOE report “Top Value Added Chemicals from Biomass” ranked succinic acid as the most promising chemical platform for biotechnology process development. Five years later, Bioamber launched the first ever commercial production plant, and made bio-based succinic acid a commercial reality.

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