Chemo-enzymatic synthesis of caprolactam using intermediates accumulated in potato.
12 / 2007 - 12 / 2010
Refinement of crude oil yields hydrocarbons as primary products, such as ethylene and benzene. The introduction of hetero atoms like nitrogen into these compounds, using reagents such as ammonia, is a cumbersome process. Conversely, many products formed in plants often already contain these types of functionality. Therefore it is attractive to exploit this feature in order to by-pass the preparation of these reagents, as well as eliminating various process steps by utilising suitable precursors formed in the plant for the production of chemicals. In this project it is proposed to accumulate 6-amino-2-ketocaproic acid in potato, and convert this to 6-aminocaproic acid to obtain a precursor for the production of e-caprolactam (used in nylon-6 production). The synthesis of e-caprolactam has been widely described and generally involves the following steps: synthesis of cyclohexanone, transformation of cyclohexanone to the corresponding oxime and Beckmann rearrangement of the oxime to e-caprolactam. The current global volume of e-caprolactam is ca. 3.5 mln tonnes at a price of ca. EUR 1500 per tonne.
Lysine is an essential amino acid which is synthesised by plants and micro-organisms. The accumulation of lysine in potato has been well investigated and described by one of us. We were able to increase lysine biosynthesis by de-regulating the feedback mechanism specifically in potato tubers via genetic modification, which resulted in a 15-fold increase of lysine content in the tubers (up to 1% of FW). The cost of lysine by traditional fermentation methods is ca. EUR 1200 per tonne. It is proposed that, using lysine accumulation in plants, the cost may be reduced to EUR 600-800 per tonne. The lysine produced in this way could be a good starting point for the synthesis of e-caprolactam precursors. A route from lysine to e-caprolactam has been described. However, in this project it is proposed that accumulation of 6-amino-2-ketocaproic acid, an intermediate in a potential e-caprolactam synthesis, may be achieved in potato tubers that already accumulate lysine and contain an extra enzyme for the conversion. By introduction of the enzyme lysine oxidase from a micro-organism into potato, lysine will be converted, leading to accumulation of 6-amino-2-ketocaproic acid. This is then isolated from potato by, e.g., ion exchange chromatography. Amino-ketocaproic acid can then be transformed to 6-aminocaproic acid. The initial reduction may be achieved chemically (e.g. H2/catalyst) or enzymatically (e.g. alcohol dehydrogenase). Dehydration should be carried out under conditions so as not to cause elimination of the amino group. Here the use of (modified) alumina may be appropriate. The final reduction step is expected to be similar to conventional hydrogenation technology. The resultant 6-aminocaproic acid can then be readily converted to e-caprolactam by known technology.
Currently there is limited description of the use of amino acids (and derivatives thereof) as raw materials for nitrogen containing industrial chemicals. The need for these kinds of processes has been identified by the European Technology Platform for Sustainable Chemistry.