New Biocatalytic Synthesis of Single Enantiomer Amino Acids: Protein and Reaction Engineering for Production of L-Glufosinate

Dr G. Matcham, Celgro, USA

Dr Matcham discussed work carried out at Celgro to produce L-glufosinate a single enantiomer form of glufosinate, which is an established, systemic herbicide sold as a racemate (>1000Tpa). The target was to develop an efficient (maximum performance, minimum cost) biocatalytic transamination of keto-acid (9) to L-glufosinate (L-GA, 10).

Although existing Celgro biocatalysts showed excellent isopropylamine conversion activity, they showed no activity with PPO, so the biocatalyst had to be modified to accept new keto-acids such as PPO as substrates. After 5 rounds of mutagenesis that started with a thermally stable isopropylamine transaminase, an active catalyst was generated. The catalyst was formulated as a stable, spray-dried powder for ease of handling. The optimised process produces 250-300g/L product in 8 hours, with 99.9% conversion of the raw material (PPO) and less than 0.1% impurities. The biocatalyst is removed by ultrafiltration and the product L-GA is produced as a technical concentrate ready for formulation. In addition this technology has also been extended so that it can be applied to the synthesis of a wide variety of both (R)- and (S)-amino acid