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)-α-amino acids, α-keto acids, (R)-α-amino acids, and (R)-β-amino acids. With cofactor recycling, protein engineering, and transformation optimization, four (S)-α-amino acids, four α-keto acids, four (R)-α-amino acids, and four (R)-β-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.
Keywords: amino group; biocatalysis; enzyme engineering; multienzyme cascade; phenylpropionic acids.
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