Efficient production of phenylpropionic acids by an amino-group-transformation biocatalytic cascade

Phenylpropionic acids are commonly used in the synthesis of pharmaceuticals, cosmetics, and fine chemicals. However, the synthesis of phenylpropionic acids faces the challenges of high cost of substrates and a limited range of products. Here, we present an artificially designed amino-group-transformation biocatalytic process, which uses simple phenols, pyruvate, and ammonia to synthesize diverse phenylpropionic acids. This biocatalytic cascade comprises an amino-group-introduction module and three amino-group-transformation modules, and operates in a modular assembly manner. Escherichia coli catalysts coexpressing enzymes from different modules achieve whole-cell simultaneous one-pot transformations of phenols into the corresponding phenylpropionic acids including (S)-alpha-amino acids, alpha-keto acids, (R)-alpha-amino acids, and (R)-beta-amino acids. With cofactor recycling, protein engineering, and transformation optimization, four (S)-alpha-amino acids, four alpha-keto acids, four (R)-alpha-amino acids, and four (R)-beta-amino acids are synthesized with good conversion (68-99%) and high enantioselectivities (>98%). Therefore, the amino-group-transformation concept provides a universal and efficient tool for synthesizing diverse products.